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39-503: An arenavirus is a bi- or trisegmented ambisense RNA virus that is a member of the family Arenaviridae . These viruses infect rodents and occasionally humans. A class of novel, highly divergent arenaviruses, properly known as reptarenaviruses, have also been discovered which infect snakes to produce inclusion body disease , mostly in boa constrictors . At least eight arenaviruses are known to cause human disease. The diseases derived from arenaviruses range in severity. Aseptic meningitis,

78-431: A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids . DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base-pairing interactions or RNA by half ladder replication. A DNA polymerase from the thermophilic bacterium, Thermus aquaticus ( Taq ) ( PDB 1BGX , EC 2.7.7.7)

117-404: A core of nucleic acid enclosed in a protein coat. Although they are categorized as negative-sense viruses, arenaviruses are ambisense . While sections of their genome encode genes in the negative sense (reverse polarity), other sections encode genes in the opposite (forward/positive sense) direction. This complex gene expression structure is theorized to be a primitive regulatory system, allowing

156-465: A host cell. Genomic sense RNA packaged into the arenavirus virion is designated negative-sense RNA, and must first be copied into a positive-sense mRNA in order to produce viral protein . The RNA segments are denoted Small (S), Medium (M; if present), and Large (L), and code for four viral proteins in a unique ambisense coding strategy. For mammarenaviruses and reptarenaviruses, each RNA segment codes for two viral proteins in opposite orientation such that

195-534: A low cost, taken orally, and able to withstand tropical climates due to the regions where these infections are occurring. For this reason high throughput screening (HTS) of small molecular libraries could be the answer to finding a better remedy. HTS collects libraries of small synthetic molecules that can be used to identify protein promoting "agonist" molecules or protein inhibiting "antagonist" interactions. With HTS sustainable antiviral drugs can be discovered against possible new human pathogenic viruses. Immunotherapy

234-403: A result of the risk of IBD before introducing them into their permanent collections and breeding programs. While the disease has not been identified in non-boid snakes, non-boid snakes can harbour the virus. Mites are thought to be the primary vector of the virus, or at least to be a contributory factor. Its distribution is worldwide, specifically in captive boid snakes. Its occurrence in the wild

273-605: A severe human disease that causes inflammation covering the brain and spinal cord, can arise from the lymphocytic choriomeningitis virus . Hemorrhagic fever syndromes, including Lassa fever , are derived from infections such as Guanarito virus , Junin virus , Lassa virus , Lujo virus , Machupo virus , Sabia virus , or Whitewater Arroyo virus . Because of the epidemiological association with rodents, some arenaviruses and bunyaviruses are designated as roboviruses . Viewed in cross-section, arenaviruses contain grainy particles that are ribosomes acquired from their host cells. It

312-402: A small RING-domain containing protein (Z). The Z protein forms homo oligomers and a structural component of the virions. The formation of these oligomers is an essential step for particle assembly and budding. Binding between Z and the viral envelope glycoprotein complex is required for virion infectivity. Z also interacts with the L and NP proteins. Polymerase activity appears to be modulated by

351-483: A vague "palm" shape, and is sometimes considered a different superfamily ( InterPro :  IPR043519 ). Primases generally don't fall into either category. Bacterial primases usually have the Toprim domain, and are related to topoisomerases and mitochondrial helicase twinkle . Archae and eukaryotic primases form an unrelated AEP family, possibly related to the polymerase palm. Both families nevertheless associate to

390-762: A wide array of extremely variable manifestations that may or may not gradually progress to death. Clinical signs may vary, with regurgitation and neurological symptoms being the most prominent in the early and later stages of its progression, respectively. In boa constrictors, the first signs may include off-and-on regurgitation followed by inappetence, and some develop head tremors. Abnormal shedding may occur. Some develop chronic regurgitation and anorexia (lack of appetite or refusal to feed). However, not all infected snakes may regurgitate. Boas lose weight and may develop clogged nares (nostrils), stomatitis , or secondary pneumonia. The disease can rapidly progress to produce nervous-system disorders, such as disorientation, corkscrewing of

429-679: Is a severe illness with hemorrhagic and neurological manifestations and a case fatality of fifteen to thirty percent. The way this virus spreads is through increased traveling to and from endemic regions. This traveling has led to the importation of Lassa fever into non-endemic metropolitan areas all over the world. A new species of arenavirus named the Lujo virus has been linked to five patients who exhibited symptoms of viral hemorrhagic fever in South Africa. The disease originated near Lusaka, Zambia and spread to Johannesburg , South Africa , after

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468-609: Is also indicated as a possibility. The snake mite, Ophionyssus natricis , has been implicated as a possible vector for the virus, since mite infestations are commonly seen in epizootics of IBD and in captive specimens of these snakes. Mites are sometimes very difficult to eradicate due to their resistance to certain toxins used to eliminate them. Permethrin is effective against mite infestations, but must be used with great caution and only in small quantities due to its toxicity to snakes. Alternative approaches include biological agents that are sprayed onto infested animals that desiccate

507-414: Is another potential approach. Monoclonal antibodies against Junin virus have been tested in animal models. An immunotherapeutic agent active against all tested mammarenaviruses that use the transferrin receptor 1 as their receptor was under investigation in 2020. Inclusion body disease All boid snakes should be considered susceptible to the disease. Many zoos quarantine boas specifically as

546-399: Is critical for efficient viral RNA synthesis, but potential interterminal double-stranded RNA interactions must be transiently relieved in order to recruit the viral polymerase . The S-segment RNA is approximately 3.5 kb, and encodes the viral nucleocapsid protein (NP) and glycoprotein (GPC). The L-segment RNA is approximately 7.2 kb, and encodes the viral RNA-dependent RNA-polymerase (L) and

585-484: Is critical for recruitment of the viral replication machinery and initiation of viral mRNA transcription and genomic replication . The conserved 5' and 3' RNA termini sequences are complementary and allows each RNA segment to adopt a double-stranded RNA panhandle structure that maintains the termini in close proximity and results in a circular appearance to purified arenavirus genomic templates visualized by electron microscopy . The double-stranded RNA panhandle structure

624-805: Is diagnostic for the disease, the absence of such inclusions does not necessarily indicate that the snake is not diseased or is free from the IBD virus. While cells having inclusions may show mild degenerative changes, inflammation is rarely seen in visceral tissues. In the brain, mild to severe encephalitis occurs, with lymphocytic perivascular cuffing. Several snakes with lymphoproliferative disorders have been identified with lymphoid infiltrates in multiple organs. The disease can be diagnosed in live snakes through blood tests. The primary route of transmission has not yet been identified, but direct contact may result in its transmission to developing embryos in viviparous species and eggs in oviparous species. Venereal transmission

663-527: Is from this characteristic that they acquired the name arena , from the Latin root meaning sand . The ribosomal structures are not believed to be essential for virus replication. Virus particles, or virions, are pleomorphic (variable in shape) but are often spherical, with a diameter of 60–300 nm, and are covered with surface glycoprotein spikes. The virus contains a beaded nucleocapsid with two single-stranded RNA segments. The nucleocapsid consists of

702-438: Is known. Snakes diagnosed with or suspected of having IBD should be euthanized because progression and transmission of the virus is both very rapid and destructive. Newly acquired snakes should be quarantined for at least 3 and preferably 6 months before being introduced into established collections. The recommended period of quarantine for any wild-caught boa or python is at least 4–6 months. Polymerase In biochemistry ,

741-412: Is unknown. The disease has only been identified in adult and subadult specimens, not neonates. Even so, all age groups are considered susceptible, and anecdotal reports of the infection in neonates have been made. A retro-like virus infection was suspected as the causative agent of IBD, but identification of highly divergent arenavirus sequences from boa constrictors with IBD suggested arenaviruses to be

780-401: Is used in the polymerase chain reaction , an important technique of molecular biology . A polymerase may be template-dependent or template-independent. Poly-A-polymerase is an example of template independent polymerase. Terminal deoxynucleotidyl transferase also known to have template independent and template dependent activities. Polymerases are generally split into two superfamilies,

819-798: The house mouse . Old and New World area viruses appear to have diverged ~45,000 years ago. The Old World Mammarenaviruses originated ~23.1-1.88 thousand years ago, most likely in Southern Africa, while the New World Mammarenaviruses evolved in the Latin America-Caribbean region ~41.4-3.3 thousand years ago. The evolution of the Mammarenavirus genus has been studied. The New World and Old World species diverged less than 45,000 years ago. The New World species evolved between 41,400 and 3,300 years ago in

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858-453: The "right hand" fold ( InterPro :  IPR043502 ) and the "double psi beta barrel " (often simply "double-barrel") fold. The former is seen in almost all DNA polymerases and almost all viral single-subunit polymerases; they are marked by a conserved "palm" domain. The latter is seen in all multi-subunit RNA polymerases, in cRdRP, and in "family D" DNA polymerases found in archaea. The "X" family represented by DNA polymerase beta has only

897-618: The Arenavirus infection is related to age, race, or sex within the degree of contact with the dried rodent excreta. All of these diseases pose a great threat to public health in the regions where it is taking place. For example, when the Old World Lassa virus turns into Lassa fever, this usually results in a significant amount of mortality. Similarly the New World Junin virus causes Argentine hemorrhagic fever. This fever

936-545: The Latin America-Caribbean region. The Old World species evolved between 23,100 and 1,880 years ago, most likely in southern Africa. Some arenaviruses are zoonotic pathogens and are generally associated with rodent —transmitted disease in humans. Each virus usually is associated with a particular rodent host species in which it is maintained. Arenaviruses persist in nature by infecting rodents first and then transmitted into humans. Humans can be infected through mucosal exposure to aerosols, or by direct contact of abraded skin with

975-465: The Ministries of Health of the two countries in various facets of the outbreak investigation, including laboratory diagnosis, investigations, active case finding and follow-up of contacts. Very few treatment methods are available. The current lack of a licensed vaccine and limited therapeutic options for the arenavirus make it arguably among the most neglected virus groups. The only licensed drug for

1014-601: The association between the L and Z proteins. Interaction between the Z and NP proteins is critical for genome packaging. The glycoprotein (GP) is synthesised as a precursor molecule. It is cleaved into three parts - GP1, GP2 and a stable signal peptide (SSP). These reactions are catalysed by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P). These processes are essential for fusion competence and incorporation of mature GP into nascent budding virion particles. Within

1053-436: The etiological agent of IBD. Cell culture isolation of several arenaviruses from boid snakes with IBD further solidified, but did not yet confirm, the etiological relationship between IBD and arenaviruses. In python species, the disease presents as a profound, highly severe neurological illness that is swiftly fatal. In adult boa constrictors, the disease assumes a milder, more chronic or, sometimes, even asymptomatic form with

1092-677: The family Arenaviridae , arenaviruses were formerly all placed in the genus Arenavirus , but in 2015 were divided into the genera Mammarenavirus for those with mammalian hosts and Reptarenavirus for those infecting snakes. Reptarenaviruses and mammarenavirus are separated by an impenetrable species barrier. Infected rodents cannot pass disease onto snakes, and IBD in captive snakes is not transmissible to humans. A third genus, Hartmanivirus (not to be confused with genus Haartmanvirus of vibrio phages in family Demerecviridae , order Caudovirales ), has also been established, including other species that infect snakes. The organisation of

1131-666: The first patient was transported to a hospital there. The results of genetic sequencing tests conducted by epidemiologists at Columbia University in New York City , USA, and at the Special Pathogens Branch of the Centers for Disease Control in Atlanta , USA, provided evidence that the causative agent of the disease is a virus from the family Arenaviridae, which ultimately resulted in the deaths of four out of

1170-619: The five infected in Zambia and South Africa during the outbreak which began in September 2008. Arenavirus has also pinpointed as the cause of death of three donor organ recipients in Australia who contracted the virus after receiving kidney and a liver donations from a single infected organ donor in late 2006. All three died in the first week of 2007. WHO and its Global Outbreak Alert and Response Network (GOARN) partners continue to support

1209-558: The genome of this genus is typical of arenaviruses but their glycoproteins resemble those of filoviruses . Species in this genus lack the matrix protein. A fourth genus, Antennavirus , has also been established to accommodate two arenaviruses found in striated frogfish ( Antennarius striatus ). A third antennavirus has been detected in Chinook salmon and sockeye salmon . Mammarenaviruses can be divided into two serogroups, which differ genetically and by geographical distribution: When

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1248-538: The head and neck, holding the head in abnormal and unnatural positions, rolling onto the back, or stargazing. Stomatitis, pneumonia, undifferentiated cutaneous sarcomas, lymphoproliferative disorders, and leukemia have all been observed in affected specimens. Burmese pythons generally show signs of central nervous system disease without manifestation of other clinical signs and regurgitation is seen only in boas. These are symptoms similar to those seen in specimens infected by Chlamydia –specifically Chlamydophila psittaci ,

1287-469: The infectious material, derived from infected rodents. Aerosols are fine mists or sprays of rodent dried excreta, especially urine that is dropped in the environment. Most of the Arenaviruses caught by humans are within their own homes when these rodents seek shelter. The virus can be caught in factories, from food that has been contaminated, or within agricultural work areas. Humans' risk of contracting

1326-441: The mites, rendering them unable to lay their eggs or consume blood beneath the scales of their host. The incubation period for mite eggs is thought to be about 10–14 days, so the treatment should be repeated after 10 days to ensure that any eggs that hatch or larvae that develop into nymphs are eliminated from the host before reaching sexual maturity and becoming able to repeat their reproduction cycle. To date, no treatment for IBD

1365-477: The negative-sense RNA genome serves as the template for transcription of a single mRNA and the positive-sense copy of the RNA genome templates a second mRNA . The separate coding sequences of the two viral proteins are divided by an intergenic region RNA sequence that is predicted to fold into a stable hairpin structure. The extreme termini of each RNA segment contains a 19 nucleotide highly conserved sequence that

1404-411: The so-called parrot's disease. Several snakes have been seen with proliferative pneumonia, while inclusions are commonly seen in the liver, kidney, and pancreas. Cases have also been observed with only very few inclusions. In a few snakes with signs of central nervous system disease, and with a severe encephalitis, no inclusions have been seen in any cells. While the presence of characteristic inclusions

1443-425: The treatment of human arenavirus infection is the nucleoside analogue ribavirin . Ribavirin reduces morbidity and mortality in humans infected with certain arenaviruses, such as LASV and JUNV infections, if it is taken in the early stages of the disease. Ribavirin displays mixed success in treating severe arenaviral disease and is associated with significant toxicities. Effective antiviral drugs need to be produced at

1482-612: The virus is classified "Old World" this means it was found in the Eastern Hemisphere in places such as Europe, Asia, and Africa. When it is found in the Western Hemisphere, in places such as Argentina, Bolivia, Venezuela, Brazil, and the United States, it is classified "New World". Lymphocytic choriomeningitis (LCM) virus is the only mammarenavirus found worldwide because of its ubiquitous Old World host,

1521-409: The virus to control what proteins are synthesized at what point in the life cycle. The life cycle of the arenavirus is restricted to the cell cytoplasm. Arenaviruses have a segmented RNA genome that consists of two single-stranded ambisense RNAs. As with all negative-sense RNA viruses, the genomic RNA alone is not infectious and the viral replication machinery is required to initiate infection within

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