161-465: The human immunodeficiency virus ( HIV ) is a retrovirus that attacks the immune system . It is a preventable disease . There is no vaccine or cure for HIV. It can be managed with treatment and become a manageable chronic health condition. While there is no cure or vaccine, antiretroviral treatment can slow the course of the disease and enable people living with HIV to lead long and healthy lives. An HIV-positive person on treatment can expect to live
322-440: A " kissing stem-loop ". Although virions of different retroviruses do not have the same morphology or biology, all the virion components are very similar. The main virion components are: The retroviral genome is packaged as viral particles. These viral particles are dimers of single-stranded, positive-sense, linear RNA molecules. Retroviruses (and orterviruses in general) follow a layout of 5'– gag – pro – pol – env –3' in
483-615: A 10- to 20-fold reduction in transmission risk. Pre-exposure prophylaxis for HIV (" PrEP ") with a daily dose of the medications tenofovir , with or without emtricitabine , is effective in people at high risk including men who have sex with men, couples where one is HIV-positive, and young heterosexuals in Africa. It may also be effective in intravenous drug users, with a study finding a decrease in risk of 0.7 to 0.4 per 100 person years. The USPSTF , in 2019, recommended PrEP in those who are at high risk. Universal precautions within
644-462: A DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm , the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backward). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point
805-459: A biopsy made in Kinshasa, in 1960, along with previously known sequences, suggested a common ancestor between 1873 and 1933 (with central estimates varying between 1902 and 1921). Genetic recombination had earlier been thought to "seriously confound" such phylogenetic analysis, but later "work has suggested that recombination is not likely to systematically bias [results]", although recombination
966-529: A brief period of influenza-like illness . During this period the person may not know that they are HIV-positive, yet they will be able to pass on the virus . Typically, this period is followed by a prolonged incubation period with no symptoms. Eventually the HIV infection increases the risk of developing other infections such as tuberculosis , as well as other opportunistic infections , and tumors which are rare in people who have normal immune function. The late stage
1127-453: A concern that insertional mutagenesis due to integration into the host genome might lead to cancer or leukemia. This is unlike Lentivirus , a genus of Retroviridae , which are able to integrate their RNA into the genome of non-dividing host cells. Two RNA genomes are packaged into each retrovirus particle, but, after an infection, each virus generates only one provirus . After infection, reverse transcription occurs and this process
1288-404: A high frequency of genital ulcers , caused by genital ulcer diseases (GUD). GUD are simply sexually transmitted diseases that cause genital ulcers; examples are syphilis , chancroid , lymphogranuloma venereum , and genital herpes . These diseases increase the probability of HIV transmission dramatically, from around 0.01–0.1% to 4–43% per heterosexual act, because the genital ulcers provide
1449-463: A high viral load and the cut was deep. In the United States, intravenous drug users made up 12% of all new cases of HIV in 2009, and in some areas more than 80% of people who inject drugs are HIV-positive. HIV is transmitted in about 90% of blood transfusions using infected blood. In developed countries the risk of acquiring HIV from a blood transfusion is extremely low (less than one in half
1610-577: A human but incapable of transmission beyond the short acute infection period) could spread in colonial cities. The simulations used parameters of sexual transmission obtained from the current HIV literature. They modelled people's 'sexual links', with different levels of sexual partner change among different categories of people (prostitutes, single women with several partners a year, married women, and men), according to data obtained from modern studies of sexual activity in African cities. The simulations let
1771-401: A long incubation period . Lentiviruses are transmitted as single-stranded, positive- sense , enveloped RNA viruses . Upon entry into the target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded reverse transcriptase that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into
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#17327648630041932-535: A million) where improved donor selection and HIV screening is performed; for example, in the UK the risk is reported at one in five million and in the United States it was one in 1.5 million in 2008. In low-income countries, only half of transfusions may be appropriately screened (as of 2008), and it is estimated that up to 15% of HIV infections in these areas come from transfusion of infected blood and blood products, representing between 5% and 10% of global infections. It
2093-399: A needle during drug injection is between 0.63% and 2.4% per act, with an average of 0.8%. The risk of acquiring HIV from a needle stick from an HIV-infected person is estimated as 0.3% (about 1 in 333) per act and the risk following mucous membrane exposure to infected blood as 0.09% (about 1 in 1000) per act. This risk may, however, be up to 5% if the introduced blood was from a person with
2254-417: A new host species if it is rapidly transmitted between hosts, while each host is still in the acute infection period. This process favors the accumulation of adaptive mutations more rapidly, therefore increasing the odds that a better adapted viral variant will appear in the host before the immune system suppresses the virus. Such better adapted variants could then survive in the human host for longer than
2415-942: A newly introduced fish virus genus are retroviruses classified as complex. These viruses have genes called accessory genes, in addition to gag, pro, pol and env genes. Accessory genes are located between pol and env, downstream from the env, including the U3 region of LTR, or in the env and overlapping portions. While accessory genes have auxiliary roles, they also coordinate and regulate viral gene expression. In addition, some retroviruses may carry genes called oncogenes or onc genes from another class. Retroviruses with these genes (also called transforming viruses) are known for their ability to quickly cause tumors in animals and transform cells in culture into an oncogenic state. The polyproteins are cleaved into smaller proteins each with their own function. The nucleotides encoding them are known as subgenes . When retroviruses have integrated their own genome into
2576-464: A normal life, and die with the virus, not of it. Effective treatment for HIV-positive people (people living with HIV ) involves a life-long regimen of medicine to suppress the virus, making the viral load undetectable. Without treatment it can lead to a spectrum of conditions including acquired immunodeficiency syndrome ( AIDS ). Treatment is recommended as soon as the diagnosis is made. An HIV-positive person who has an undetectable viral load as
2737-616: A portal of viral entry, and contain many activated T cells expressing the CCR5 co-receptor, the main cell targets of HIV. Sousa et al. use molecular dating techniques to estimate the time when each HIV group split from its closest SIV lineage. Each HIV group necessarily crossed to humans between this time and the time when it started to spread (the time of the MRCA ), because after the MRCA certainly all lineages were already in humans, and before
2898-611: A process of cell-to-cell spread. The hybrid spreading mechanisms of HIV contribute to the virus' ongoing replication against antiretroviral therapies. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was originally discovered (and initially referred to also as LAV or HTLV-III). It is more virulent , more infective , and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 as compared with HIV-1 implies that fewer people exposed to HIV-2 will be infected per exposure. Because of its relatively poor capacity for transmission, HIV-2
3059-529: A rare strain found only in a few Cameroonian people (group N) are clearly derived from SIVcpz strains endemic in Pan troglodytes troglodytes chimpanzee populations living in Cameroon . Another very rare HIV-1 strain (group P) is clearly derived from SIVgor strains of Cameroon. Finally, the primate ancestor of HIV-1 group O, a strain infecting 100,000 people mostly from Cameroon but also from neighbouring countries,
3220-523: A result of harsh conditions, forced labor, displacement, and unsafe injection and vaccination practices associated with colonialism , particularly in French Equatorial Africa . The workers in plantations, construction projects, and other colonial enterprises were supplied with bushmeat , which would have contributed to an increase in hunting and, it follows, a higher incidence of human exposure to SIV. Several historical sources support
3381-427: A result of long-term treatment has effectively no risk of transmitting HIV sexually. Campaigns by UNAIDS and organizations around the world have communicated this as Undetectable = Untransmittable . Without treatment the infection can interfere with the immune system , and eventually progress to AIDS , sometimes taking many years. Following initial infection an individual may not notice any symptoms, or may experience
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#17327648630043542-580: A significant increase compared to previous years. Two main clinical staging systems are used to classify HIV and HIV-related disease for surveillance purposes: the WHO disease staging system for HIV infection and disease , and the CDC classification system for HIV infection . The CDC's classification system is more frequently adopted in developed countries. Since the WHO's staging system does not require laboratory tests, it
3703-403: A time of rapid urbanisation and colonisation in equatorial Africa. Exactly when the zoonosis occurred is not known. Some molecular dating studies suggest that HIV-1 group M had its most recent common ancestor (MRCA) (that is, started to spread in the human population) in the early 20th century, probably between 1915 and 1941. A study published in 2008, analyzing viral sequences recovered from
3864-482: A vaginal gel containing tenofovir (a reverse transcriptase inhibitor ) immediately before sex seems to reduce infection rates by approximately 40% among African women. By contrast, use of the spermicide nonoxynol-9 may increase the risk of transmission due to its tendency to cause vaginal and rectal irritation. Circumcision in sub-Saharan Africa "reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months". Owing to these studies, both
4025-431: Is "expected to increase variance". The results of a 2008 phylogenetics study support the later work and indicate that HIV evolves "fairly reliably". Further research was hindered due to the primates being critically endangered. Sample analyses resulted in little data due to the rarity of experimental material. The researchers, however, were able to hypothesize a phylogeny from the gathered data. They were also able to use
4186-427: Is a retrovirus. This virus passes to newborn mice through mammary milk. When they are 6 months old, the mice carrying the virus get mammary cancer because of the retrovirus. In addition, leukemia virus I (HTLV-1), found in human T cell, has been found in humans for many years. It is estimated that this retrovirus causes leukemia in the ages of 40 and 50. It has a replicable structure that can induce cancer. In addition to
4347-450: Is accompanied by recombination . Recombination involves template strand switching between the two genome copies (copy choice recombination) during reverse transcription. From 5 to 14 recombination events per genome occur at each replication cycle. Genetic recombination appears to be necessary for maintaining genome integrity and as a repair mechanism for salvaging damaged genomes. The DNA formed after reverse transcription (the provirus)
4508-536: Is also believed to carry an increased risk of HIV transmission as condoms are rarely worn, physical trauma to the vagina or rectum is likely, and there may be a greater risk of concurrent sexually transmitted infections. The second-most frequent mode of HIV transmission is via blood and blood products. Blood-borne transmission can be through needle-sharing during intravenous drug use, needle-stick injury, transfusion of contaminated blood or blood product, or medical injections with unsterilized equipment. The risk from sharing
4669-462: Is also the fact that, while both HIV-1 and HIV-2 attain substantial viral loads in the human organism, adventitious SIV infecting humans seldom does so: people with SIV antibodies often have very low or even undetectable SIV viral load . This suggests that both HIV-1 and HIV-2 are adapted to humans, and serial passage could have been the process responsible for it. Marx et al. proposed that unsterile injections (that is, injections where
4830-527: Is at least tens of thousands of years old). Several of the theories of HIV origin accept the established knowledge of the HIV/SIV phylogenetic relationships, and also accept that bushmeat practice was the most likely cause of the initial transfer to humans. All of them propose that the simultaneous epidemic emergences of four HIV groups in the late 19th-early 20th century, and the lack of previous known emergences, are explained by new factor(s) that appeared in
4991-472: Is called acute HIV, primary HIV or acute retroviral syndrome. Many individuals develop an illness like influenza , mononucleosis or glandular fever 2–4 weeks after exposure while others have no significant symptoms. Symptoms occur in 40–90% of cases and most commonly include fever , large tender lymph nodes , throat inflammation , a rash , headache, tiredness, and/or sores of the mouth and genitals. The rash, which occurs in 20–50% of cases, presents itself on
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5152-709: Is caused by a human immunodeficiency virus (HIV), which originated in non-human primates in Central and West Africa . While various sub-groups of the virus acquired human infectivity at different times, the present pandemic had its origins in the emergence of one specific strain – HIV-1 subgroup M – in Léopoldville in the Belgian Congo (now Kinshasa in the Democratic Republic of the Congo ) in
5313-648: Is defined as an HIV infection with either a CD4 T cell count below 200 cells per μL or the occurrence of specific diseases associated with HIV infection. In the absence of specific treatment, around half of people infected with HIV develop AIDS within ten years. The most common initial conditions that alert to the presence of AIDS are pneumocystis pneumonia (40%), cachexia in the form of HIV wasting syndrome (20%), and esophageal candidiasis . Other common signs include recurrent respiratory tract infections . Opportunistic infections may be caused by bacteria , viruses , fungi , and parasites that are normally controlled by
5474-493: Is equally poor. Comprehensive sexual education provided at school may decrease high-risk behavior. A substantial minority of young people continues to engage in high-risk practices despite knowing about HIV/AIDS, underestimating their own risk of becoming infected with HIV. Voluntary counseling and testing people for HIV does not affect risky behavior in those who test negative but does increase condom use in those who test positive. Enhanced family planning services appear to increase
5635-588: Is especially high, estimated as 1.4–1.7% per act in both heterosexual and homosexual contacts. While the risk of transmission from oral sex is relatively low, it is still present. The risk from receiving oral sex has been described as "nearly nil"; however, a few cases have been reported. The per-act risk is estimated at 0–0.04% for receptive oral intercourse. In settings involving prostitution in low-income countries, risk of female-to-male transmission has been estimated as 2.4% per act, and of male-to-female transmission as 0.05% per act. Risk of transmission increases in
5796-583: Is largely confined to West Africa . After the virus enters the body, there is a period of rapid viral replication , leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles per milliliter of blood. This response is accompanied by a marked drop in the number of circulating CD4 T cells . The acute viremia is almost invariably associated with activation of CD8 T cells , which kill HIV-infected cells, and subsequently with antibody production, or seroconversion . The CD8 T cell response
5957-506: Is longer than the RNA genome because each of the terminals have the U3 - R - U5 sequences called long terminal repeat (LTR). Thus, 5' terminal has the extra U3 sequence, while the other terminal has the U5 sequence. LTRs are able to send signals for vital tasks to be carried out such as initiation of RNA production or management of the rate of transcription. This way, LTRs can control replication, hence,
6118-404: Is lymphoma, which is the cause of death of nearly 16% of people with AIDS and is the initial sign of AIDS in 3% to 4%. Both these cancers are associated with human herpesvirus 8 (HHV-8). Cervical cancer occurs more frequently in those with AIDS because of its association with human papillomavirus (HPV). Conjunctival cancer (of the layer that lines the inner part of eyelids and the white part of
6279-541: Is not yet explained why only four HIV groups ( HIV-1 groups M and O, and HIV-2 groups A and B) spread considerably in human populations, despite bushmeat practices being widespread in Central and West Africa, and the resulting human SIV infections being common. It also remains unexplained why all epidemic HIV groups emerged in humans nearly simultaneously, and only in the 20th century, despite very old human exposure to SIV (a 2010 phylogenetic study demonstrated that SIV
6440-514: Is now commonly used to describe a cancer-causing virus. This family now includes the following genera: Note that according to ICTV 2017, genus Spumavirus has been divided into five genera, and its former type species Simian foamy virus is now upgraded to genus Simiispumavirus with not less than 14 species, including new type species Eastern chimpanzee simian foamy virus . Both families in Group VII have DNA genomes contained within
6601-528: Is often also associated with unintended weight loss . Without treatment a person living with HIV can expect to live for 11 years. Early testing can show if treatment is needed to stop this progression and to prevent infecting others. HIV is spread primarily by unprotected sex (including anal and vaginal sex ), contaminated hypodermic needles or blood transfusions , and from mother to child during pregnancy , delivery, or breastfeeding. Some bodily fluids, such as saliva, sweat, and tears, do not transmit
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6762-562: Is possible to acquire HIV from organ and tissue transplantation , although this is rare because of screening . Unsafe medical injections play a role in HIV spread in sub-Saharan Africa . In 2007, between 12% and 17% of infections in this region were attributed to medical syringe use. The World Health Organization estimates the risk of transmission as a result of a medical injection in Africa at 1.2%. Risks are also associated with invasive procedures, assisted delivery, and dental care in this area of
6923-408: Is recommended for those at high risk, which includes anyone diagnosed with a sexually transmitted illness. In many areas of the world, a third of HIV carriers only discover they are infected at an advanced stage of the disease when AIDS or severe immunodeficiency has become apparent. Most people infected with HIV develop seroconverted (antigen-specific) antibodies within three to twelve weeks after
7084-416: Is referred to as post-exposure prophylaxis (PEP). The use of the single agent zidovudine reduces the risk of an HIV infection five-fold following a needle-stick injury. As of 2013, the prevention regimen recommended in the United States consists of three medications— tenofovir , emtricitabine and raltegravir —as this may reduce the risk further. PEP treatment is recommended after a sexual assault when
7245-539: Is spread by three main routes: sexual contact , significant exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission ). There is no risk of acquiring HIV if exposed to feces , nasal secretions, saliva, sputum , sweat, tears, urine, or vomit unless these are contaminated with blood. It is also possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection . The most frequent mode of transmission of HIV
7406-465: Is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences, the two systems allow a comparison for statistical purposes. The World Health Organization first proposed a definition for AIDS in 1986. Since then, the WHO classification has been updated and expanded several times, with the most recent version being published in 2007. The WHO system uses
7567-455: Is thought to be important in controlling virus levels, which peak and then decline, as the CD4 T cell counts recover. A good CD8 T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus. Ultimately, HIV causes AIDS by depleting CD4 T cells. This weakens the immune system and allows opportunistic infections . T cells are essential to
7728-463: Is through sexual contact with an infected person. However, an HIV-positive person who has an undetectable viral load as a result of long-term treatment has effectively no risk of transmitting HIV sexually, known as Undetectable = Untransmittable . The existence of functionally noncontagious HIV-positive people on antiretroviral therapy was controversially publicized in the 2008 Swiss Statement , and has since become accepted as medically sound. Globally,
7889-543: Is translated into molecules of the capsid protein, and for the pol gene; it is translated into molecules of reverse transcriptase. Retroviruses need a lot more of the Gag proteins than the Pol proteins and have developed advanced systems to synthesize the required amount of each. As an example, after Gag synthesis nearly 95 percent of the ribosomes terminate translation, while other ribosomes continue translation to synthesize Gag–Pol. In
8050-627: The African AIDS crisis . Beatrice Hahn , Paul M. Sharp , and their colleagues proposed that "[the epidemic emergence of HIV] most likely reflects changes in population structure and behaviour in Africa during the 20th century and perhaps medical interventions that provided the opportunity for rapid human-to-human spread of the virus". After the Scramble for Africa started in the 1880s, European colonial powers established cities, towns, and other colonial stations. A largely masculine labor force
8211-512: The Baltimore classification system, which groups viruses together based on their manner of messenger RNA synthesis, they are classified into two groups: Group VI: single-stranded RNA viruses with a DNA intermediate in their life cycle, and Group VII: double-stranded DNA viruses with an RNA intermediate in their life cycle. All members of Group VI use virally encoded reverse transcriptase , an RNA-dependent DNA polymerase, to produce DNA from
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#17327648630048372-487: The Ivory Coast . These HIV-2 strains are probably dead-end infections , and each of them is most closely related to SIVsmm strains from sooty mangabeys living in the same country where the human infection was found. Molecular dating studies suggest that both the epidemic groups (A and B) started to spread among humans between 1905 and 1961 (with the central estimates varying between 1932 and 1945). According to
8533-653: The Republic of the Congo , and the Central African Republic . HIV-2 is less transmissible and is largely confined to West Africa, along with its closest relative, a virus of the sooty mangabey ( Cercocebus atys atys ), an Old World monkey inhabiting southern Senegal , Guinea-Bissau , Guinea , Sierra Leone , Liberia , and western Ivory Coast . Research in this area is conducted using molecular phylogenetics , comparing viral genomic sequences to determine relatedness. Scientists generally accept that
8694-639: The T cells of a human host. The discovery of the main HIV/SIV phylogenetic relationships permits explaining broad HIV biogeography : the early centres of the HIV-1 groups were in Central Africa, where the primate reservoirs of the related SIVcpz and SIVgor viruses ( chimpanzees and gorillas ) exist; similarly, the HIV-2 groups had their centres in West Africa, where sooty mangabeys , which harbour
8855-616: The World Health Organization (WHO) African Region. HIV/AIDS is considered a pandemic —a disease outbreak which is present over a large area and is actively spreading. The United States' National Institutes of Health (NIH) and the Gates Foundation have pledged $ 200 million focused on developing a global cure for AIDS. There are three main stages of HIV infection: acute infection, clinical latency, and AIDS. The initial period following infection with HIV
9016-427: The germ line , their genome is passed on to a following generation. These endogenous retroviruses (ERVs), contrasted with exogenous ones, now make up 5–8% of the human genome. Most insertions have no known function and are often referred to as " junk DNA ". However, many endogenous retroviruses play important roles in host biology, such as control of gene transcription, cell fusion during placental development in
9177-471: The molecular clock of a specific strain of HIV to determine the initial date of transmission, which is estimated to be around 1915–1931. Similar research has been undertaken with SIV strains collected from several wild sooty mangabey ( Cercocebus atys atys ) (SIVsmm) populations of the West African nations of Sierra Leone , Liberia, and Ivory Coast . The resulting phylogenetic analyses show that
9338-496: The serial passage process alone would be associated with strong natural selection . David Gisselquist proposed that the mass injection campaigns to treat trypanosomiasis ( sleeping sickness ) in Central Africa were responsible for the emergence of HIV-1. Unlike Marx et al. , Gisselquist argued that the millions of unsafe injections administered during these campaigns were sufficient to spread rare HIV infections into an epidemic, and that evolution of HIV through serial passage
9499-423: The 1880s). Thus, this theory also potentially explains why HIV emerged only after the late 19th century. Uli Linke has argued that the practice of female genital mutilation (either or both of clitoridectomy and infibulation) is responsible for the high incidence of AIDS in Africa, since intercourse with a female who has undergone clitoridectomy is conducive to exchange of blood. Male circumcision may reduce
9660-481: The 1920s. There are two types of HIV: HIV-1 and HIV-2 . HIV-1 is more virulent, more easily transmitted, and it is the cause of the vast majority of HIV infections globally. The pandemic strain of HIV-1 is closely related to a virus found in chimpanzees of the subspecies Pan troglodytes troglodytes , which live in the forests of the Central African nations of Cameroon , Equatorial Guinea , Gabon ,
9821-547: The 1920s. Kinshasa also experienced the earliest retroactive diagnosis of HIV, in the LEO70 sample, which was isolated from a preserved plasma sample of "an adult Bantu male" who also had a Sickle cell trait and G6PDD taken in 1959. It is also believed that passengers riding on the region's Belgian railway trains were able to spread the virus to larger areas, combining with the active sex trade, rapid population growth and unsterilized needles used in health clinics to create what became
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#17327648630049982-453: The CD4 T cell count rises to above 200 per μL of blood or other AIDS-defining illnesses are cured. Consistent condom use reduces the risk of HIV transmission by approximately 80% over the long term. When condoms are used consistently by a couple in which one person is infected, the rate of HIV infection is less than 1% per year. There is some evidence to suggest that female condoms may provide an equivalent level of protection. Application of
10143-591: The Central African cities over time. Sousa et al. charts reveal that male circumcision frequencies were much lower in several cities of western and central Africa in the early 20th century than they are currently. The reason is that many ethnic groups not performing circumcision by that time gradually adopted it, to imitate other ethnic groups and enhance the social acceptance of their boys ( colonialism produced massive intermixing between African ethnic groups). About 15–30% of men in Léopoldville and Douala in
10304-513: The Democratic Republic of Congo was the main centre of HIV-1 group M, a virus descended from SIVcpz strains of a subspecies ( Pan troglodytes troglodytes ) that does not exist in this country. It is clear that the several HIV-1 and HIV-2 strains descend from SIVcpz, SIVgor, and SIVsmm viruses, and that bushmeat practice provides the most plausible cause of cross-species transfer to humans. However, some loose ends remain. It
10465-608: The French Equatorial Africa federation of colonies, in Equatorial Guinea (then a Spanish colony), or in Cameroon (which was a German colony between 1884 and 1916, and then fell to Allied forces in World War I, and had most of its area administered by France, in close association with French Equatorial Africa). This theory was later dubbed "Heart of Darkness" by Jim Moore, alluding to the book of
10626-420: The HIV life cycle . Combination of several (typically three or four) antiretroviral drugs is known as highly active antiretroviral therapy (HAART). Feline leukemia virus and Feline immunodeficiency virus infections are treated with biologics , including the only immunomodulator currently licensed for sale in the United States, Lymphocyte T-Cell Immune Modulator (LTCI). History of HIV AIDS
10787-486: The RNA genome. gag and pol encode polyproteins, each managing the capsid and replication. The pol region encodes enzymes necessary for viral replication, such as reverse transcriptase, protease and integrase. Depending on the virus, the genes may overlap or fuse into larger polyprotein chains. Some viruses contain additional genes. The lentivirus genus, the spumavirus genus, the HTLV / bovine leukemia virus (BLV) genus, and
10948-682: The RNA to DNA transcription processes used by retroviruses may have first caused DNA to be used as genetic material. In this model, the RNA world hypothesis , cellular organisms adopted the more chemically stable DNA when retroviruses evolved to create DNA from the RNA templates. An estimate of the date of evolution of the foamy-like endogenous retroviruses placed the time of the most recent common ancestor at > 450 million years ago . Gammaretroviral and lentiviral vectors for gene therapy have been developed that mediate stable genetic modification of treated cells by chromosomal integration of
11109-570: The World Health Organization and UNAIDS recommended male circumcision in 2007 as a method of preventing female-to-male HIV transmission in areas with high rates of HIV. However, whether it protects against male-to-female transmission is disputed, and whether it is of benefit in developed countries and among men who have sex with men is undetermined. Programs encouraging sexual abstinence do not appear to affect subsequent HIV risk. Evidence of any benefit from peer education
11270-560: The absence of treatment will eventually progress to AIDS, a small proportion (about 5%) retain high levels of CD4 T cells ( T helper cells ) without antiretroviral therapy for more than five years. These individuals are classified as "HIV controllers" or long-term nonprogressors (LTNP). Another group consists of those who maintain a low or undetectable viral load without anti-retroviral treatment, known as "elite controllers" or "elite suppressors". They represent approximately 1 in 300 infected persons. Acquired immunodeficiency syndrome (AIDS)
11431-494: The absence of treatment, the risk of transmission before or during birth is around 20%, and in those who also breastfeed 35%. Treatment decreases this risk to less than 5%. Antiretrovirals when taken by either the mother or the baby decrease the risk of transmission in those who do breastfeed. If blood contaminates food during pre-chewing it may pose a risk of transmission. If a woman is untreated, two years of breastfeeding results in an HIV/AIDS risk in her baby of about 17%. Due to
11592-549: The animal can result in SIV infection. Rural Africans who were not keen to pursue agricultural practices in the jungle turned to non-domesticated animals as their primary source of meat. This over-exposure to bushmeat and malpractice of butchery increased blood-to-blood contact, which then increased the probability of transmission. A recent serological survey showed that human infections by SIV are not rare in Central Africa:
11753-588: The body. The reason for the preferential loss of mucosal CD4 T cells is that the majority of mucosal CD4 T cells express the CCR5 protein which HIV uses as a co-receptor to gain access to the cells, whereas only a small fraction of CD4 T cells in the bloodstream do so. A specific genetic change that alters the CCR5 protein when present in both chromosomes very effectively prevents HIV-1 infection. HIV seeks out and destroys CCR5 expressing CD4 T cells during acute infection. A vigorous immune response eventually controls
11914-404: The cell nucleus and integrated into the cellular DNA by a virally encoded integrase and host co-factors. Once integrated, the virus may become latent , allowing the virus and its host cell to avoid detection by the immune system. Alternatively, the virus may be transcribed , producing new RNA genomes and viral proteins that are packaged and released from the cell as new virus particles that begin
12075-507: The cities of Cameroon and Ivory Coast , where HIV-1 group O and HIV-2 respectively evolved. Therefore, the peak GUD incidences in cities have a good temporal coincidence with the period when all main HIV groups crossed to humans and started to spread. In addition, the authors gathered evidence that syphilis and the other GUDs were, like injections, absent from the densely forested areas of Central and West Africa before organized colonialism socially disrupted these areas (starting in
12236-521: The concomitant high frequency of genital ulcer diseases (such as syphilis ) in nascent colonial cities. In 2014, a study conducted by scientists from the University of Oxford and the University of Leuven , in Belgium, revealed that because approximately one million people every year would flow through the prominent city of Kinshasa, which served as the origin of the first suspected HIV cases in
12397-399: The course of the germination of an embryo , and resistance to exogenous retroviral infection. Endogenous retroviruses have also received special attention in the research of immunology -related pathologies, such as autoimmune diseases like multiple sclerosis , although endogenous retroviruses have not yet been proven to play any causal role in this class of disease. While transcription
12558-409: The disruption of cellular proto-oncogenes. Rous sarcoma virus contains the src gene that triggers tumor formation. Later it was found that a similar gene in cells is involved in cell signaling, which was most likely excised with the proviral DNA. Nontransforming viruses can randomly insert their DNA into proto-oncogenes, disrupting the expression of proteins that regulate the cell cycle. The promoter of
12719-495: The early oral polio vaccines were contaminated with a chimpanzee virus, leading to the Central African outbreak. In most non-human primate species, natural SIV infection does not cause a fatal disease (but see below). Comparison of the gene sequence of SIV with HIV should, therefore, provide information about the factors necessary to cause disease in humans. The factors that determine the virulence of HIV as compared to most SIVs are only now being elucidated. Non-human SIVs contain
12880-615: The early 1980s, HIV/AIDS has had a large impact on society, both as an illness and as a source of discrimination . The disease also has large economic impacts . There are many misconceptions about HIV/AIDS , such as the belief that it can be transmitted by casual non-sexual contact. The disease has become subject to many controversies involving religion , including the Catholic Church's position not to support condom use as prevention. It has attracted international medical and political attention as well as large-scale funding since it
13041-461: The early 20th century (when the colonial abuses and forced labor were at their peak). Later research established that these theories were mostly correct: HIV-1 groups M and O started to spread in humans in late 19th–early 20th century. In addition, all groups of HIV-1 descend from either SIVcpz or SIVgor from apes living to the west of the Ubangi River , either in countries that belonged to
13202-411: The early 20th century should be uncircumcised, and these cities were the probable centers of HIV-1 groups M and O, respectively. The authors studied early circumcision frequencies in 12 cities of Central and West Africa, to test if this variable correlated with HIV emergence. This correlation was strong for HIV-2 : among 6 West African cities that could have received immigrants infected with SIVsmm,
13363-422: The end of this stage many people experience fever, weight loss, gastrointestinal problems and muscle pains. Between 50% and 70% of people also develop persistent generalized lymphadenopathy , characterized by unexplained, non-painful enlargement of more than one group of lymph nodes (other than in the groin) for over three to six months. Although most HIV-1 infected individuals have a detectable viral load and in
13524-419: The entire progress of the viral cycle. Although located in the nucleus, the non-integrated retroviral cDNA is a very weak substrate for transcription. For this reason, an integrated provirus is a necessary for permanent and an effective expression of retroviral genes. This DNA can be incorporated into host genome as a provirus that can be passed on to progeny cells. The retrovirus DNA is inserted at random into
13685-471: The established knowledge on this topic. However, although later research disproved some of the claims made about retroviruses, there are several controversial figures who continue to make claims which overall are considered to not have any valid basis or consensus in support of these claims. Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV . Different classes of antiretroviral drugs act on different stages of
13846-404: The existing ethnographic literature for patterns of male circumcision and hunting of apes and monkeys for bushmeat , focusing on the period 1880–1960, and on most of the 318 ethnic groups living in Central and West Africa. They also collected censuses and other literature showing the ethnic composition of colonial cities in this period. Then, they estimated the circumcision frequencies of
14007-455: The eye) is also more common in those with HIV. Additionally, people with AIDS frequently have systemic symptoms such as prolonged fevers, sweats (particularly at night), swollen lymph nodes, chills, weakness, and unintended weight loss . Diarrhea is another common symptom, present in about 90% of people with AIDS. They can also be affected by diverse psychiatric and neurological symptoms independent of opportunistic infections and cancers. HIV
14168-404: The fact that the gene sequences that code for the protease and the reverse transcriptase quickly mutate. These changes in bases cause specific codons and sites with the enzymes to change and thereby avoid drug targeting by losing the sites that the drug actually targets. Because reverse transcription lacks the usual proofreading of DNA replication, a retrovirus mutates very often. This enables
14329-460: The first 2.5 months of an HIV infection, a person's infectiousness is twelve times higher due to the high viral load associated with acute HIV. If the person is in the late stages of infection, rates of transmission are approximately eightfold greater. Commercial sex workers (including those in pornography ) have an increased likelihood of contracting HIV. Rough sex can be a factor associated with an increased risk of transmission. Sexual assault
14490-466: The following categories: The U.S. Centers for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008 and 2014. This system classifies HIV infections based on CD4 count and clinical symptoms, and describes the infection in five groups. In those greater than six years of age it is: For surveillance purposes, the AIDS diagnosis still stands even if, after treatment,
14651-435: The form of independent particles of retroviruses, consist of enveloped particles about 100 nm in diameter. The outer lipid envelope consists of glycoprotein. The virions also contain two identical single-stranded RNA molecules 7–10 kilobases in length. The two molecules are present as a dimer, formed by base pairing between complementary sequences. Interaction sites between the two RNA molecules have been identified as
14812-412: The generation and insertion of new copies of retrotransposons into the host genome. These inserts are transcribed by enzymes of the host into new RNA molecules that enter the cytosol. Next, some of these RNA molecules are translated into viral proteins. The proteins encoded by the gag and pol genes are translated from genome-length mRNAs into Gag and Gag–Pol polyproteins. In example, for the gag gene; it
14973-414: The geographical correlation found, the authors propose that it could have had an indirect role, either by increasing genital ulcer disease itself (it is known that syphilis , chancroid , and several other GUDs have higher incidences in uncircumcised men), or by permitting further spread of the HIV strain, after the first chains of sexual transmission permitted adaptation to the human organism. One of
15134-422: The gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4 T cell numbers. Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4 T cell loss occurs during the first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in
15295-411: The health care environment are believed to be effective in decreasing the risk of HIV. Intravenous drug use is an important risk factor, and harm reduction strategies such as needle-exchange programs and opioid substitution therapy appear effective in decreasing this risk. A course of antiretrovirals administered within 48 to 72 hours after exposure to HIV-positive blood or genital secretions
15456-496: The host genome. Because of this, it can be inserted into oncogenes . In this way some retroviruses can convert normal cells into cancer cells. Some provirus remains latent in the cell for a long period of time before it is activated by the change in cell environment. Studies of retroviruses led to the first demonstrated synthesis of DNA from RNA templates, a fundamental mode for transferring genetic material that occurs in both eukaryotes and prokaryotes . It has been speculated that
15617-420: The human immune system such as CD4 T cells, macrophages and dendritic cells . It directly and indirectly destroys CD4 T cells. HIV is a member of the genus Lentivirus , part of the family Retroviridae . Lentiviruses share many morphological and biological characteristics. Many species of mammals are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with
15778-433: The immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4 T cell depletion differs in the acute and chronic phases. During the acute phase, HIV-induced cell lysis and killing of infected cells by CD8 T cells accounts for CD4 T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with
15939-647: The immune response to ongoing HIV replication. It is also linked to the breakdown of the immune surveillance system of the gastrointestinal mucosal barrier caused by the depletion of mucosal CD4 T cells during the acute phase of disease. HIV/AIDS is diagnosed via laboratory testing and then staged based on the presence of certain signs or symptoms . HIV screening is recommended by the United States Preventive Services Task Force for all people 15 years to 65 years of age, including all pregnant women. Additionally, testing
16100-494: The immune system. Which infections occur depends partly on what organisms are common in the person's environment. These infections may affect nearly every organ system . People with AIDS have an increased risk of developing various viral-induced cancers, including Kaposi's sarcoma , Burkitt's lymphoma , primary central nervous system lymphoma , and cervical cancer . Kaposi's sarcoma is the most common cancer, occurring in 10% to 20% of people with HIV. The second-most common cancer
16261-405: The increased risk of death without breastfeeding in many areas in the developing world, the World Health Organization recommends either exclusive breastfeeding or the provision of safe formula. All women known to be HIV-positive should be taking lifelong antiretroviral therapy. HIV is the cause of the spectrum of disease known as HIV/AIDS. HIV is a retrovirus that primarily infects components of
16422-427: The infection and initiates the clinically latent phase. CD4 T cells in mucosal tissues remain particularly affected. Continuous HIV replication causes a state of generalized immune activation persisting throughout the chronic phase. Immune activation, which is reflected by the increased activation state of immune cells and release of pro-inflammatory cytokines , results from the activity of several HIV gene products and
16583-463: The initial infection. Diagnosis of primary HIV before seroconversion is done by measuring HIV- RNA or p24 antigen . Positive results obtained by antibody or PCR testing are confirmed either by a different antibody or by PCR. Antibody tests in children younger than 18 months are typically inaccurate, due to the continued presence of maternal antibodies . Thus HIV infection can only be diagnosed by PCR testing for HIV RNA or DNA, or via testing for
16744-430: The initial virion RNA genome. This DNA is often integrated into the host genome, as in the case of retroviruses and pseudoviruses , where it is replicated and transcribed by the host. Group VI includes: The family Retroviridae was previously divided into three subfamilies ( Oncovirinae , Lentivirinae , and Spumavirinae ), but are now divided into two: Orthoretrovirinae and Spumaretrovirinae . The term oncovirus
16905-513: The invading virus particles. The DNA genome is transcribed into both mRNA, for use as a transcript in protein synthesis, and pre-genomic RNA, for use as the template during genome replication. Virally encoded reverse transcriptase uses the pre-genomic RNA as a template for the creation of genomic DNA. Group VII includes: The latter family is closely related to the newly proposed whilst families Belpaoviridae , Metaviridae , Pseudoviridae , Retroviridae , and Caulimoviridae constitute
17066-486: The known strains (or groups) of HIV-1 are most closely related to the simian immunodeficiency viruses (SIVs) endemic in wild ape populations of West Central African forests. In particular, each of the known HIV-1 strains is either closely related to the SIV that infects the chimpanzee subspecies Pan troglodytes troglodytes (SIVcpz) or closely related to the SIV that infects western lowland gorillas , called SIVgor. The pandemic HIV-1 strain (group M or Main) and
17227-418: The late 19th century, they seek to explain why all HIV groups also started after that. The theories centred on the role of parenteral risks, such as unsterile injections, transfusions , or smallpox vaccinations are accepted as plausible by most scientists of the field. Discredited HIV/AIDS origins theories include several iatrogenic theories, such as the polio vaccine hypothesis which argues that
17388-502: The lifetime of each person. The authors suggested that the very high prevalence of the Hepatitis C virus in southern Cameroon and forested areas of French Equatorial Africa (around 40–50%) can be better explained by the unsterile injections used to treat yaws , because this disease was much more prevalent than syphilis , trypanosomiasis , and leprosy in these areas. They suggested that all these parenteral risks caused not only
17549-410: The likelihood of women with HIV using contraception, compared to basic services. It is not known whether treating other sexually transmitted infections is effective in preventing HIV. Antiretroviral treatment among people with HIV whose CD4 count ≤ 550 cells/μL is a very effective way to prevent HIV infection of their partner (a strategy known as treatment as prevention, or TASP). TASP is associated with
17710-546: The main advantages of this theory is stressed by the authors: "It [the theory] also offers a conceptual simplicity because it proposes as causal factors for SIV adaptation to humans and initial spread the very same factors that most promote the continued spread of HIV nowadays: promiscuous [sic] sex, particularly involving sex workers, GUD, and possibly lack of circumcision." Iatrogenic theories propose that medical interventions were responsible for HIV origins. By proposing factors that only appeared in Central and West Africa after
17871-465: The major risk factors at play in HIV emergence (see above), Marx et al. enunciated the underlying mechanisms in greater detail, and wrote the first review of the injection campaigns made in colonial Africa. Central to the Marx et al. argument is the concept of adaptation by serial passage (or serial transmission): an adventitious virus (or other pathogen ) can increase its biological adaptation to
18032-534: The many common infectious diseases with similar symptoms. Someone with an unexplained fever who may have been recently exposed to HIV should consider testing to find out if they have been infected. The initial symptoms are followed by a stage called clinical latency, asymptomatic HIV, or chronic HIV. Without treatment, this second stage of the natural history of HIV infection can last from about three years to over 20 years (on average, about eight years). While typically there are few or no symptoms at first, near
18193-416: The massive spread of Hepatitis C but also the spread of other pathogens , and the emergence of HIV-1 : "the same procedures could have exponentially amplified HIV-1, from a single hunter/cook occupationally infected with SIVcpz to several thousand patients treated with arsenicals or other drugs, a threshold beyond which sexual transmission could prosper." They do not suggest specifically serial passage as
18354-454: The mechanism of adaptation. According to Pépin's 2011 book, The Origins of AIDS , the virus can be traced to a central African bush hunter in 1921, with colonial medical campaigns using improperly sterilized syringe and needles playing a key role in enabling a future epidemic. Pépin concludes that AIDS spread silently in Africa for decades, fueled by urbanization and prostitution since the initial cross-species infection. Pépin also claims that
18515-479: The mid-1930s, people's movements were more tightly controlled, and mass surveys and treatments (of arsenicals and other drugs) were organized, and so the GUD incidences started to decline. They declined even further after World War II, because of the heavy use of antibiotics , so that, by the late 1950s, Léopoldville (which is the probable center of HIV-1 group M) had a very low GUD incidence. Similar processes happened in
18676-651: The most common mode of HIV transmission is via sexual contacts between people of the opposite sex ; however, the pattern of transmission varies among countries. As of 2017, most HIV transmission in the United States occurred among men who had sex with men (82% of new HIV diagnoses among males aged 13 and older and 70% of total new diagnoses). In the US, gay and bisexual men aged 13 to 24 accounted for an estimated 92% of new HIV diagnoses among all men in their age group and 27% of new diagnoses among all gay and bisexual men. With regard to unprotected heterosexual contacts, estimates of
18837-445: The most likely implicated in the origin of HIV because, by these times (roughly in the period 1950 to 1970), injection intensity in Africa was maximal. They argued that a serial passage chain of 3 or 4 transmissions between humans is an unlikely event (the probability of transmission after a needle reuse is something between 0.3% and 2%, and only a few people have an acute SIV infection at any time), and so HIV emergence may have required
18998-407: The natural transfer theory (also called "hunter theory" or "bushmeat theory"), in the "simplest and most plausible explanation for the cross-species transmission" of SIV or HIV (post mutation), the virus was transmitted from an ape or monkey to a human when a hunter was cut or otherwise injured while hunting or butchering an infected animal. The resulting exposure to blood or other bodily fluids of
19159-472: The needle or syringe is reused without sterilization or cleaning between uses), which were likely very prevalent in Africa, during both the colonial period and afterwards, provided the mechanism of serial passage that permitted HIV to adapt to humans, therefore explaining why it emerged epidemically only in the 20th century. Marx et al. emphasize the massive number of injections administered in Africa after antibiotics were introduced (around 1950) as being
19320-438: The next section). In addition, they proposed that the conditions of extreme stress associated with forced labor could depress the immune system of workers, therefore prolonging the primary acute infection period of someone newly infected by SIV, thus increasing the odds of both adaptation of the virus to humans, and of further transmissions. The authors proposed that HIV-1 originated in the area of French Equatorial Africa in
19481-424: The order Ortervirales . Endogenous retroviruses are not formally included in this classification system, and are broadly classified into three classes, on the basis of relatedness to exogenous genera: Retroviruses have been the focus of several recent claims and assertions which have been largely discredited by the science community. An initial study in 2009 seemed to make new findings which might change some of
19642-415: The p24 antigen. Much of the world lacks access to reliable PCR testing, and people in many places simply wait until either symptoms develop or the child is old enough for accurate antibody testing. In sub-Saharan Africa between 2007 and 2009, between 30% and 70% of the population were aware of their HIV status. In 2009, between 3.6% and 42% of men and women in sub-Saharan countries were tested; this represented
19803-486: The parameters (city size, proportion of people married, GUD frequency, male circumcision frequency, and transmission parameters) vary, and explored several scenarios. Each scenario was run 1,000 times, to test the probability of SIV generating long chains of sexual transmission. The authors postulated that such long chains of sexual transmission were necessary for the SIV strain to adapt better to humans, becoming an HIV capable of further epidemic emergence. The main result
19964-727: The patients received many (often more than 10) injections per year, therefore increasing the odds of SIV serial passage . Jacques Pépin and Annie-Claude Labbé reviewed the colonial health reports of Cameroon and French Equatorial Africa for the period 1921–59, calculating the incidences of the diseases requiring intravenous injections. They concluded that trypanosomiasis , leprosy , yaws , and syphilis were responsible for most intravenous injections. Schistosomiasis , tuberculosis , and vaccinations against smallpox represented lower parenteral risks: schistosomiasis cases were relatively few; tuberculosis patients only became numerous after mid-century; and there were few smallpox vaccinations in
20125-529: The percentage of people showing seroreactivity to antigens —evidence of current or past SIV infection—was 2.3% among the general population of Cameroon , 7.8% in villages where bushmeat is hunted or used, and 17.1% in the most exposed people of these villages. How the SIV virus would have transformed into HIV after infection of the hunter or bushmeat handler from the ape/monkey is still a matter of debate, although natural selection would favour any viruses capable of adjusting so that they could infect and reproduce in
20286-422: The perpetrator is known to be HIV-positive, but is controversial when their HIV status is unknown. The duration of treatment is usually four weeks and is frequently associated with adverse effects—where zidovudine is used, about 70% of cases result in adverse effects such as nausea (24%), fatigue (22%), emotional distress (13%) and headaches (9%). Retrovirus A retrovirus is a type of virus that inserts
20447-537: The plasma membrane after further glycosylation. It is important to note that a retrovirus must "bring" its own reverse transcriptase in its capsid , otherwise it is unable to utilize the enzymes of the infected cell to carry out the task, due to the unusual nature of producing DNA from RNA. Industrial drugs that are designed as protease and reverse-transcriptase inhibitors are made such that they target specific sites and sequences within their respective enzymes. However these drugs can quickly become ineffective due to
20608-448: The presence of many sexually transmitted infections and genital ulcers . Genital ulcers increase the risk approximately fivefold. Other sexually transmitted infections, such as gonorrhea , chlamydia , trichomoniasis , and bacterial vaginosis , are associated with somewhat smaller increases in risk of transmission. The viral load of an infected person is an important risk factor in both sexual and mother-to-child transmission. During
20769-498: The probability of HIV acquisition by men . Leaving aside blood transfusions , the highest HIV-1 transmissibility ever measured was from female prostitutes with 85% prevalence of HIV to uncircumcised men with GUD—"A cumulative 43% ... seroconverted to HIV-1 after a single sexual exposure." There was no seroconversion in the absence of male GUD. Sousa et al. reasoned that the adaptation and epidemic emergence of each HIV group may have required such extreme conditions, and thus reviewed
20930-437: The provirus DNA can also cause over expression of regulatory genes. Retroviruses can cause diseases such as cancer and immunodeficiency. If viral DNA is integrated into host chromosomes, it can lead to permanent infections. It is therefore important to discover the body's response to retroviruses. Exogenous retroviruses are especially associated with pathogenic diseases. For example, mice have mouse mammary tumor virus (MMTV), which
21091-519: The ranges of chimpanzees , gorillas and sooty mangabeys , and found that genital ulcer diseases (GUDs) peaked in the colonial cities during their early growth period (up to 1935). The colonial authorities recruited men to work in railways, fluvial and sea ports, and other infrastructure projects, and most of these men did not bring their wives with them. Then, the highly male-biased sex ratio favoured prostitution, which in its turn caused an explosion of GUD (especially syphilis and chancroid ). After
21252-596: The related SIVsmm virus, exist. However, these relationships do not explain more detailed patterns of biogeography, such as why epidemic HIV-2 groups (A and B) only evolved in the Ivory Coast , which is one of only six countries harbouring the sooty mangabey. It is also unclear why the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes schweinfurthii (inhabiting the Democratic Republic of Congo , Central African Republic, Rwanda , Burundi, Uganda , and Tanzania ) did not spawn an epidemic HIV-1 strain to humans, while
21413-407: The relevant African regions in that timeframe. These new factor(s) would have acted either to increase human exposures to SIV, to help it to adapt to the human organism by mutation (thus enhancing its between-humans transmissibility), or to cause an initial burst of transmissions crossing an epidemiological threshold, and therefore increasing the probability of continued spread. Genetic studies of
21574-430: The replication cycle anew. HIV is now known to spread between CD4 T cells by two parallel routes: cell-free spread and cell-to-cell spread, i.e. it employs hybrid spreading mechanisms. In the cell-free spread, virus particles bud from an infected T cell, enter the blood/extracellular fluid and then infect another T cell following a chance encounter. HIV can also disseminate by direct transmission from one cell to another by
21735-785: The retroviral DNA is referred to as a provirus . The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds. Retroviruses have many subfamilies in three basic groups. The specialized DNA-infiltration enzymes in retroviruses make them valuable research tools in molecular biology, and they have been used successfully in gene delivery systems. Evidence from endogenous retroviruses (inherited provirus DNA in animal genomes) suggests that retroviruses have been infecting vertebrates for at least 450 million years. Virions , viruses in
21896-485: The risk of HIV transmission per sexual act appear to be four to ten times higher in low-income countries than in high-income countries. In low-income countries, the risk of female-to-male transmission is estimated as 0.38% per act, and of male-to-female transmission as 0.30% per act; the equivalent estimates for high-income countries are 0.04% per act for female-to-male transmission, and 0.08% per act for male-to-female transmission. The risk of transmission from anal intercourse
22057-483: The rough endoplasmic reticulum glycosylation begins and the env gene is translated from spliced mRNAs in the rough endoplasmic reticulum, into molecules of the envelope protein. When the envelope protein molecules are carried to the Golgi complex, they are divided into surface glycoprotein and transmembrane glycoprotein by a host protease. These two glycoprotein products stay in close affiliation, and they are transported to
22218-488: The same title written by Joseph Conrad , the main focus of which is colonial abuses in equatorial Africa. In several articles published since 2001, Preston Marx, Philip Alcabes, and Ernest Drucker proposed that HIV emerged because of rapid serial human-to-human transmission of SIV (after a bushmeat hunter or handler became SIV-infected) through unsafe or unsterile injections. Although both Chitnis et al. and Sharp et al. also suggested that this may have been one of
22379-412: The short acute infection period, in high numbers (high viral load ), which would grant it more possibilities of epidemic spread. Marx et al. reported experiments of cross-species transfer of SIV in captive monkeys (some of which made by themselves), in which the use of serial passage helped to adapt SIV to the new monkey species after passage by three or four animals. In agreement with this model
22540-415: The split with the closest simian strain, the lineage was in a simian. HIV-1 groups M and O split from their closest SIVs around 1931 and 1915, respectively. This information, together with the datations of the HIV groups' MRCAs, mean that all HIV groups likely crossed to humans in the early 20th century. The authors reviewed colonial medical articles and archived medical reports of the countries at or near
22701-783: The transferred vector genomes. This technology is of use, not only for research purposes, but also for clinical gene therapy aiming at the long-term correction of genetic defects, e.g., in stem and progenitor cells. Retroviral vector particles with tropism for various target cells have been designed. Gammaretroviral and lentiviral vectors have so far been used in more than 300 clinical trials, addressing treatment options for various diseases. Retroviral mutations can be developed to make transgenic mouse models to study various cancers and their metastatic models . Retroviruses that cause tumor growth include Rous sarcoma virus and mouse mammary tumor virus . Cancer can be triggered by proto-oncogenes that were mistakenly incorporated into proviral DNA or by
22862-475: The trunk and is maculopapular , classically. Some people also develop opportunistic infections at this stage. Gastrointestinal symptoms, such as vomiting or diarrhea may occur. Neurological symptoms of peripheral neuropathy or Guillain–Barré syndrome also occur. The duration of the symptoms varies, but is usually one or two weeks. These symptoms are not often recognized as signs of HIV infection. Family doctors or hospitals can misdiagnose cases as one of
23023-419: The two cities from the Ivory Coast studied ( Abidjan and Bouaké ) had much higher frequency of uncircumcised men (60–85%) than the others, and epidemic HIV-2 groups emerged initially in this country only. This correlation was less clear for HIV-1 in Central Africa. Sousa et al. then built computer simulations to test if an 'ill-adapted SIV' (meaning a simian immunodeficiency virus already infecting
23184-405: The usual gene sequence of retroviruses, HTLV-1 contains a fourth region, PX. This region encodes Tax, Rex, p12, p13 and p30 regulatory proteins. The Tax protein initiates the leukemic process and organizes the transcription of all viral genes in the integrated HTLV proviral DNA. Exogenous retroviruses are infectious RNA- or DNA-containing viruses that are transmitted from one organism to another. In
23345-413: The very high frequency of injections of the antibiotic era. The molecular dating studies place the initial spread of the epidemic HIV groups before that time (see above). According to Marx et al. , these studies could have overestimated the age of the HIV groups, because they depend on a molecular clock assumption, may not have accounted for the effects of natural selection in the viruses, and
23506-545: The view that bushmeat hunting indeed increased, both because of the necessity to supply workers and because firearms became more widely available. The colonial authorities also gave many vaccinations against smallpox , and injections, of which many would be made without sterilising the equipment between uses. Chitnis et al. proposed that both these parenteral risks and the prostitution associated with forced labor camps could have caused serial transmission (or serial passage ) of SIV between humans (see discussion of this in
23667-479: The virus suggested in 2008 that the most recent common ancestor of the HIV-1 M group dates back to the Belgian Congo city of Léopoldville (modern Kinshasa ), circa 1910. Proponents of this dating link the HIV epidemic with the emergence of colonialism and growth of large colonial African cities, leading to social changes, including a higher degree of non-monogamous sexual activity, the spread of prostitution , and
23828-486: The virus to grow resistant to antiviral pharmaceuticals quickly, and impedes the development of effective vaccines and inhibitors for the retrovirus. One difficulty faced with some retroviruses, such as the Moloney retrovirus, involves the requirement for cells to be actively dividing for transduction. As a result, cells such as neurons are very resistant to infection and transduction by retroviruses. This gives rise to
23989-487: The virus was brought to the Americas by a Haitian teacher returning home from Zaire in the 1960s. Sex tourism and contaminated blood transfusion centers ultimately propelled AIDS to public consciousness in the 1980s and a worldwide pandemic. João Dinis de Sousa, Viktor Müller, Philippe Lemey, and Anne-Mieke Vandamme proposed that HIV became epidemic through sexual serial transmission, in nascent colonial cities, helped by
24150-459: The virus. Oral sex has little risk of transmitting the virus. Ways to avoid catching HIV and preventing the spread include safe sex , treatment to prevent infection (" PrEP "), treatment to stop infection in someone who has been recently exposed (" PEP "), treating those who are infected , and needle exchange programs . Disease in a baby can often be prevented by giving both the mother and child antiretroviral medication . Recognized worldwide in
24311-682: The viruses most closely related to the two strains of HIV-2 that spread considerably in humans (HIV-2 groups A and B) are the SIVsmm found in the sooty mangabeys of the Tai forest, in western Ivory Coast . There are six additional known HIV-2 groups, each having been found in just one person. They all seem to derive from independent transmissions from sooty mangabeys to humans. Groups C and D have been found in two people from Liberia , groups E and F have been discovered in two people from Sierra Leone , and groups G and H have been detected in two people from
24472-476: The world. People giving or receiving tattoos , piercings , and scarification are theoretically at risk of infection but no confirmed cases have been documented. It is not possible for mosquitoes or other insects to transmit HIV. HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk, resulting in the baby also contracting HIV. As of 2008, vertical transmission accounted for about 90% of cases of HIV in children. In
24633-481: Was accompanied by unprecedented increase in people's movements. Michael Worobey and colleagues observed that the growth of cities probably played a role in the epidemic emergence of HIV, since the phylogenetic dating of the two older strains of HIV-1 (groups M and O), suggest that these viruses started to spread soon after the main Central African colonial cities were founded. Amit Chitnis, Diana Rawls, and Jim Moore proposed that HIV may have emerged epidemically as
24794-549: Was classically thought to occur only from DNA to RNA, reverse transcriptase transcribes RNA into DNA. The term "retro" in retrovirus refers to this reversal (making DNA from RNA) of the usual direction of transcription. It still obeys the central dogma of molecular biology , which states that information can be transferred from nucleic acid to nucleic acid but cannot be transferred back from protein to either protein or nucleic acid. Reverse transcriptase activity outside of retroviruses has been found in almost all eukaryotes , enabling
24955-584: Was confirmed in 2006 to be SIVgor. The pandemic HIV-1 group M is most closely related to the SIVcpz collected from the southeastern rain forests of Cameroon (modern East Province ) near the Sangha River . Thus, this region is presumably where the virus was first transmitted from chimpanzees to humans. However, reviews of the epidemiological evidence of early HIV-1 infection in stored blood samples, and of old cases of AIDS in Central Africa, have led many scientists to believe that HIV-1 group M early human centre
25116-422: Was hastily recruited to work in fluvial and sea ports, railways, other infrastructures, and in plantations. This disrupted traditional tribal values and favored casual sexual activity with an increased number of partners. In the nascent cities women felt relatively liberated from rural tribal rules and many remained unmarried or divorced during long periods, this being rare in African traditional societies. This
25277-630: Was identified in the 1980s. HIV made the jump from other primates to humans in west-central Africa in the early-to-mid-20th century. AIDS was first recognized by the U.S. Centers for Disease Control and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the early part of the decade. Between the first time AIDS was readily identified through 2024, the disease is estimated to have caused at least 42.3 million deaths worldwide. In 2023, 630,000 people died from HIV-related causes, an estimated 1.3 million people acquired HIV and about 39.9 million people worldwide living with HIV, 65% of whom are in
25438-498: Was not an important factor. The authors propose that these findings explain the temporal patterns of HIV emergence: no HIV emerging in tens of thousands of years of human slaughtering of apes and monkeys , several HIV groups emerging in the nascent, GUD-riddled, colonial cities, and no epidemically successful HIV group emerging in mid-20th century, when GUD was more controlled, and cities were much bigger. Male circumcision had little to moderate effect in their simulations, but, given
25599-418: Was not essential to the emergence of the HIV epidemic in the 20th century. This theory focuses on injection campaigns that peaked in the period 1910–40, that is, around the time the HIV-1 groups started to spread. It also focuses on the fact that many of the injections in these campaigns were intravenous (which are more likely to transmit SIV/HIV than subcutaneous or intramuscular injections), and many of
25760-486: Was probably not in Cameroon, but rather further south in the Democratic Republic of the Congo (then the Belgian Congo ), more probably in its capital city, Kinshasa (formerly Léopoldville). Using HIV-1 sequences preserved in human biological samples along with estimates of viral mutation rates, scientists calculate that the jump from chimpanzee to human probably happened during the late 19th or early 20th century,
25921-452: Was that genital ulcer frequency was by far the most decisive factor. For the GUD levels prevailing in Léopoldville in the early 20th century, long chains of SIV transmission had a high probability. For the lower GUD levels existing in the same city in the late 1950s (see above), they were much less likely. And without GUD (a situation typical of villages in forested equatorial Africa before colonialism ) SIV could not spread at all. City size
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