98-463: Human foamy virus Human foamy virus ( HFV ) is a retrovirus in the genus Spumavirus . The spumaviruses are complex and significantly different from the other six genera of retroviruses in several ways. The foamy viruses derive their name from the characteristic ‘foamy’ appearance of the cytopathic effect (CPE) induced in the cells. Foamy virus in humans occurs only as a result of zoonotic infection . The first description of foamy virus (FV)
196-440: 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
294-453: 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
392-506: A different group of researchers claimed that SFVcpz(hu) was not a distinct type of FV but rather a variant strain of chimpanzee FV. The debate came to an end in 1994 when the virus was cloned and sequenced. The sequencing showed that there are 86–95% identical amino acids between the SFV and the one isolated from the Kenyan patient. In addition, phylogenetic analysis showed that the pol regions of
490-566: A few years. The weakness of the muscles involved in swallowing may lead to swallowing difficulty ( dysphagia ). Typically, this means that some food may be left in the mouth after an attempt to swallow, or food and liquids may regurgitate into the nose rather than go down the throat ( velopharyngeal insufficiency ). Weakness of the muscles that move the jaw ( muscles of mastication ) may cause difficulty chewing. In individuals with MG, chewing tends to become more tiring when chewing tough, fibrous foods. Difficulty in swallowing, chewing, and speaking
588-454: A gene therapy vector is that since it buds from an intracellular membrane ( endoplasmic reticulum membrane); it results in low extracellular titers of the viral vector. Retrovirus A retrovirus is a type of virus that inserts 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 ,
686-451: A human nasopharyngeal carcinoma (NPC) from a Kenyan patient. The agent was termed a human FV because of its origin, and named SFVcpz(hu) as the prototypic laboratory strain. The SFV came from its similarity to simian foamy virus (SFV). Not long after this, a group of researchers concluded that it was a distinct type of FV and most closely related to SFV types 6 and 7, both of which were isolated from chimpanzees. In another report, however,
784-1081: A life-threatening myasthenia crisis which must be treated by prolonged mechanical ventilation. In a study of 795 MG patients undergoing surgical removal of their thymus under general anesthesia, sugammadex , a neuromuscular-blocking drug (i.e., a drug that reverses neuromuscular blockade) significantly reduced the development of this crisis. These studies suggest that inhalation anesthetics are best avoided in MG patients but if used close post-operation monitoring should be conducted for MG patients being anesthetized with these agents and sugammadex should be considered for routine use in MG patients anesthetized with these agents who undergo thymectomy or other types of surgery. Glucocorticoids : Glucocorticoids are anti-inflammatory agents that in initial studies were used at high dosages and found to worsen MG in 25-75% of cases. However, further studies found that glucocorticoids do have favorable effects on MG when taken long-term. Two glucocorticoids, oral prednisone and prednisolone , are now
882-449: A muscle-specific kinase. Other, less frequent antibodies are found against LRP4 , agrin , and titin proteins. Human leukocyte antigen haplotypes are associated with increased susceptibility to myasthenia gravis and other autoimmune disorders. Relatives of people with myasthenia gravis have a higher percentage of other immune disorders. The thymus gland cells form part of the body's immune system. In those with myasthenia gravis,
980-460: A myasthenic crisis, a paralysis of the respiratory muscles occurs, necessitating assisted ventilation to sustain life. Crises may be triggered by various biological stressors such as infection, fever, an adverse reaction to medication, or emotional stress. Antibiotics : In the macrolide family of antibiotics , azithromycin , telithromycin (which is no longer available in the U.S. market), and erythromycin are reported to exacerbate MG. In
1078-462: A natural habitat in Kenya and thus was most likely the origin of this SFV variant, and the virus was probably acquired as a zoonotic infection . Most of the differences between the spumaviruses and the other retroviruses come from the life cycle. Some of the main differences are that FV buds from the endoplasmic reticulum instead of the plasma membrane; this difference gives FV a unique morphology. FV
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#17327906147571176-942: 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
1274-426: A paraneoplastic syndrome (typically older patients) or associated with a non-cancerous primary autoimmune condition (typically younger patients). It usually involves lower limb weakness and exercise-induced fatiguability, although the upper limbs and eyes may also be involved. Lambert's sign is the unusual improvement of grip strength that follows after squeezing the hand at maximum intensity for 2–3 seconds. Treatment
1372-469: A rat model of human MG. These studies suggest that procainamide as well as other type Ia antiarrhythmic agents should be avoided or used with extreme caution in MG patients. Depolarizing neuromuscular blockers : Depolarizing neuromuscular blockers suppress the neurons' signaling at neuromuscular junctions thereby reducing the affected skeletal muscles contractibility. These blockers are used as muscle relaxants in patients undergoing surgery. Succinylcholine
1470-540: A review of 169 patients who were reported to develop MG or had worsened MG symptoms while taking a statin (i.e., simvastatin , atorvastatin , rosuvastatin , pravastatin , lovastatin , or fluvastatin ), 138 had developed generalized MG, 13 had developed ocular MG, and 18 had worsening of their MG. Following discontinuance of the statin and treatment of their MG, 63 patients fully recovered, 27 patients were recovering, 19 patients had not yet recovered, 5 patients recovered but had ongoing symptoms, 1 patient had died, and there
1568-1235: A specific body part without loss of consciousness. There are two broad classes of these anesthetics: esters (i.e., procaine , cocaine , tetracaine benzocaine , and chloroprocaine ) and amides (i.e. lidocaine , bupivacaine , etidocaine , levobupivacaine , mepivacaine , prilocaine , and ropivacaine ). Ester local anesthetics are metabolized by pseudocholinesterases which in MG patients taking anticholinesterase drugs may lead to excessive levels of these ester anesthetics. Amide local anesthetics are not metabolized by psuedocholineesterases. Based on these considerations, amide local anesthetics are strongly preferred over ester local anesthetics in patients with MG. Other Drugs: Rare cases of MG exacerbations have been reported in patients treated with: 1) penicillins , i.e., ampicillin and amoxicillin ; 2) anti-cancer medications, i.e., lorlatinib , nilotinib , imatinib (these three drugs are tyrosine kinase inhibitors that may also cause MG), dabrafenib , and trametinib ; 3) antipsychotic drugs, i.e., chlorpromazine , pimozide , thioridazine , clozapine , olanzapine , haloperidol , quetiapine , risperidone , and olanzapine ; 4) IFN-α (may also cause MG); and 5)
1666-446: A stable packaging cell line. Having this would possibly reduce the need for a replication-competent helper virus. Other advantages are human to human transmission has never been reported, it has a safer spectrum of insertional mutagenesis than other retroviruses, and since there are two promoters in the genome, it may be possible to make a vector that expresses the foreign genes under the control of both promoters. A disadvantage of HFV as
1764-491: A total 5,898 patients who received these drugs, 52 developed new onset MG and 11 had a flare of their preexisting MG. The symptoms of MG developed within 6 days to 16 weeks (median time 4 weeks). Their medicine-induced MG symptoms were often severe with 29 patients developing respiratory failure that required mechanical ventilation . Other studies have reported that these checkpoint inhibitors cause respiratory failure in 45% and death in 25–40% of patients. These medications, it
1862-409: Is a distinct condition from myasthenia gravis. It is an adult-onset, autoimmune condition affecting the neuromuscular junction. However, it lacks eye abnormalities and is associated with autoimmune conditions such as systemic lupus erythematosus, Hashimoto's thyroiditis, and thymoma. Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune condition that attacks the neuromuscular junction, either as
1960-401: Is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness . The most commonly affected muscles are those of the eyes , face , and swallowing. It can result in double vision , drooping eyelids , and difficulties in talking and walking. Onset can be sudden. Those affected often have a large thymus or develop a thymoma . Myasthenia gravis
2058-427: 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
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#17327906147572156-543: Is a symptom shared by other neuromuscular diseases. Most of the metabolic myopathies , such as McArdle disease (GSD-V), have abnormal muscle fatigue rather than fixed muscle weakness. Also, like myasthenia gravis, exercise intolerance in McArdle disease improves with regular physical activity (performed safely using activity adaptations such as getting into second wind , the "30 for 80 rule," and "six second rule"). A small minority of patients with McArdle disease also have
2254-450: 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)
2352-533: Is an autoimmune disease of the neuromuscular junction which results from antibodies that block or destroy nicotinic acetylcholine receptors (AChR) at the junction between the nerve and muscle . This prevents nerve impulses from triggering muscle contractions. Most cases are due to immunoglobulin G1 (IgG1) and IgG3 antibodies that attack AChR in the postsynaptic membrane, causing complement-mediated damage and muscle weakness. Rarely, an inherited genetic defect in
2450-507: Is characterized by an immature looking core with an electron lucent center with glycoprotein spikes on the surface. FV replication more closely resembles the Hepadnaviridae , which are another family of reverse transcriptase encoding viruses. Reverse transcription of the genome occurs at a later step in the replication cycle, which results in the infectious particles having DNA rather than RNA , this also leads to less integration in
2548-476: Is characterized by exclusively ocular symptoms, droopy eyelids, or double vision. Generalized MG has muscle weakness with a variable combination of the bulbar, axial, or limb and respiratory muscles. Patients can also be sub-grouped by the age of onset: juvenile-onset MG (onset age ≤ 18 years of age), early-onset MG (EOMG; 19–50 years of age), late-onset MG (LOMG; onset > 50 years of age), and very late-onset (VLOMG; onset age ≥ 65 years of age). The subgroup of
2646-533: Is considered to be the most sensitive (although not the most specific) test for MG, a thin needle electrode is inserted into different areas of a particular muscle to record the action potentials from several samplings of different individual muscle fibers. Two muscle fibers belonging to the same motor unit are identified, and the temporal variability in their firing patterns is measured. Frequency and proportion of particular abnormal action potential patterns, called "jitter" and "blocking", are diagnostic. Jitter refers to
2744-399: Is generally treated with medications known as acetylcholinesterase inhibitors , such as neostigmine and pyridostigmine . Immunosuppressants , such as prednisone or azathioprine , may also be used. The surgical removal of the thymus may improve symptoms in certain cases. Plasmapheresis and high-dose intravenous immunoglobulin may be used during sudden flares of the condition. If
2842-506: 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,
2940-446: Is no longer typically performed, as its use can lead to life-threatening bradycardia (slow heart rate) which requires immediate emergency attention. Production of edrophonium was discontinued in 2008. A chest X-ray may identify widening of the mediastinum suggestive of thymoma, but computed tomography or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas and are generally done for this reason. MRI of
3038-514: 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
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3136-436: Is suggested, are best avoided in MG patients, particularly in patients who previously had a life-threatening reaction to them. If these medications must be used in MG patients, it is recommended that the patients be pre-treated with a glucocorticoid , plasmapheresis , or intravenous immunoglobulin to reduce the chances of their developing severe symptoms. Statins : Statins are drugs that lower blood cholesterol levels. In
3234-411: Is the first symptom in about one-sixth of individuals. Weakness of the muscles involved in speaking may lead to dysarthria and hypophonia . Speech may be slow and slurred, or have a nasal quality . In some cases, a singing hobby or profession must be abandoned. Due to weakness of the muscles of facial expression and muscles of mastication, facial weakness may manifest as the inability to hold
3332-529: Is the only depolarizing neuromuscular blocker available in the U.S. market. Succinylcholine's ability to induce or worsen MG is unclear. It has been suggested to cause life-threatening side effects such as rhabdomyolysis , myotonia , and hyperkalemia in patients with muscle disease although the role of succinylcholine in causing these side effects also remains unclear. Until more evidence on these issues becomes available and since there are other neuromuscular blocking agents without these deleterious side effects,
3430-460: Is thought to be inhibited at the lower temperature, which is the basis for this diagnostic test. This generally is performed on the eyelids when ptosis is present and is deemed positive if a ≥2-mm rise in the eyelid occurs after the ice is removed. This test requires the intravenous administration of edrophonium chloride or neostigmine, drugs that block the breakdown of acetylcholine by cholinesterase (acetylcholinesterase inhibitors). This test
3528-543: 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
3626-512: 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
3724-474: The extraocular muscles ). Eye symptoms tend to get worse when watching television, reading, or driving, particularly in bright conditions. Consequently, some affected individuals choose to wear sunglasses. The term "ocular myasthenia gravis" describes a subtype of MG where muscle weakness is confined to the eyes, i.e. extraocular muscles, m. levator palpebrae superioris, and m. orbicularis oculi . Typically, this subtype evolves into generalized MG, usually after
3822-415: The fluoroquinolone antibiotic family, ciprofloxacin , norfloxacin , ofloxacin , and moxifloxacin are reported to exacerbate MG. And, In the aminoglycoside family of antibiotics, gentamicin , streptomycin , and neomycin are reported to exacerbate MG. The aminoglycoside tobramycin has not been reported to exacerbate MG and may be used in patients that require aminoglycoside treatment. Because of
3920-427: 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
4018-432: The neuromuscular junction results in a similar condition known as congenital myasthenia . Babies of mothers with myasthenia may have symptoms during their first few months of life, known as neonatal myasthenia or more specifically transient neonatal myasthenia gravis . Diagnosis can be supported by blood tests for specific antibodies, the edrophonium test , electromyography (EMG), or a nerve conduction study . MG
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4116-585: The second and third trimesters . Complete remission can occur in some mothers. Immunosuppressive therapy should be maintained throughout pregnancy, as this reduces the chance of neonatal muscle weakness, and controls the mother's myasthenia. About 10–20% of infants with mothers affected by the condition are born with transient neonatal myasthenia gravis (TNMG), which generally produces feeding and respiratory difficulties that develop about 12 hours to several days after birth. A child with TNMG typically responds very well to acetylcholinesterase inhibitors, and
4214-643: The FV Env protein also contains an endoplasmic reticulum retention signal which is part of why the virus buds from the endoplasmic reticulum. Another area of difference between FV and other retroviruses is the possibility of recycling the core once the virus is in the cell. Persistence in the absence of disease, but in the presence of antibodies is a defining characteristic of FV infection. HFV has been isolated from patients with various neoplastic and degenerative diseases such as myasthenia gravis , multiple sclerosis , De Quervain's thyroiditis , and Graves’ disease but
4312-556: 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). Myasthenia gravis Myasthenia gravis ( MG )
4410-486: 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
4508-682: 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
4606-426: The abnormal variation in the time interval between action potentials of adjacent muscle fibers in the same motor unit. Blocking refers to the failure of nerve impulses to elicit action potentials in adjacent muscle fibers of the same motor unit. Applying ice for 2–5 minutes to the muscles reportedly has a sensitivity and specificity of 76.9% and 98.3%, respectively, for the identification of MG. Acetylcholinesterase
4704-583: The age of 40 and in men over the age of 60. It is uncommon in children. With treatment, most live to an average life expectancy . The word is from the Greek mys , "muscle" and asthenia "weakness", and the Latin gravis , "serious". The initial, main symptom in MG is painless weakness of specific muscles, not fatigue. The muscle weakness becomes progressively worse ( fatigue ) during periods of physical activity and improves after periods of rest. Typically,
4802-423: The autoantibody profile includes AChR seropositive, MuSK seropositive, LRP4 seropositive, and agrin seropositive. During a physical examination to check for MG, a doctor might ask the person to perform repetitive movements. For instance, the doctor may ask one to look at a fixed point for 30 seconds and to relax the muscles of the forehead, because a person with MG and ptosis of the eyes might be involuntarily using
4900-404: The breathing muscles become significantly weak, mechanical ventilation may be required. Once intubated acetylcholinesterase inhibitors may be temporarily held to reduce airway secretions. MG affects 50 to 200 people per million. It is newly diagnosed in 3 to 30 people per million each year. Diagnosis has become more common due to increased awareness. MG most commonly occurs in women under
4998-611: 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
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#17327906147575096-596: The chance of having a severe reaction to the corticosteroids. Calcium channel blockers : Calcium channel blockers (e.g., felodipine , nifedipine , and verapamil ) are drugs that lower blood pressure in patients with hypertension . Felodipine and nifedipine are reported to worsen MG and nifedipine and verapamil are reported to cause respiratory failure in patients with severe generalized MG. MG patients, especially those who are in remission or have well-controlled disease, generally can be treated with these blockers using their lowest effective doses and close monitoring for
5194-421: The chemical element, lithium . These agents can be used in MG patients because reports on their exacerbation (or induction) of MG are rare. MG is an autoimmune synaptopathy . The disorder occurs when the immune system malfunctions and generates antibodies that attack the body's tissues. The antibodies in MG attack a normal human protein, the nicotinic acetylcholine receptor, or a related protein called MuSK ,
5292-1365: The comorbidity of ptosis (drooping upper eyelid). Late-onset GSD-II ( Pompe disease ) and GSD-XV also have muscle weakness or fatigue with comorbidities of ptosis and ophthalmoplegia; as do many of the mitochondrial myopathies . Other diseases that involve abnormal muscle fatigue (which may be described as exercise-induced muscle weakness, reversible muscle weakness, or muscle weakness that improves with rest) include: endocrine myopathies (such as Hoffman syndrome ), Tubular aggregate myopathy (TAM), ischemia (such as intermittent claudication , popliteal artery entrapment syndrome , and chronic venous insufficiency ), and poor diet or malabsorption diseases that lead to vitamin D deficiency (osteomalic myopathy). Although limb-girdle muscular dystrophies (LGMDs) involve fixed muscle weakness, LGMDR8 also involves muscle fatigue; as do some limb-girdle muscular dystrophy-dystroglycanopathies such as MDDGC3 (a.k.a. LGMDR15 and LGMD2O). Myofibrillar myopathy 10, dimethylglycine dehydrogenase deficiency, erythrocyte lactate transporter defect, and myopathy with myalgia, increased serum creatine kinase, with or without episodic rhabdomyolysis (MMCKR) also include muscle fatigue. X-linked episodic muscle weakness (EMWX) includes general muscle weakness, ptosis, and fluctuations in strength. In some individuals, fatiguability
5390-544: The complex retroviruses exclusively express transcripts from the LTR. The structural genes of FV are another one of its unique features. The Gag protein is not efficiently cleaved into the mature virus which lends to the immature morphology. The Pol precursor protein is only partially cleaved; the integrase domain is removed by viral protease. As in other retroviruses, the Env protein is cleaved into surface and transmembrane domains but
5488-649: The condition generally resolves over a period of three weeks, as the antibodies diminish, and generally does not result in any complications. However, a small percentage of fetuses and newborns with TNMG, particularly those who have antibodies directed against the fetal form of the AChR (their disorder is a subtype of TNMG termed the "acetylcholine receptor inactivation syndrome") have a more severe form of TNMG which includes weakness in skeletal muscles regulating breathing, respiratory failure, and various deformities such as arthrogryposis multiplex congenita . In some of these cases,
5586-399: 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
5684-469: The cranium and orbits may also be performed to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles. The forced vital capacity may be monitored at intervals to detect increasing muscular weakness. Acutely, negative inspiratory force may be used to determine adequacy of ventilation; it is performed on those individuals with MG. The muscle weakness that worsens with activity (abnormal muscle fatigue ) in myasthenia gravis
5782-425: The cytoplasmic solubility of APOBEC3G . The tas gene, however, is required for replication. It encodes a protein that functions in transactivating the long terminal repeat (LTR) promoter. FV has a second promoter, the internal promoter (IP) which is located in the env gene. The IP drives expression of the tas and bet genes. The IP is also unique in that the virus has the capacity to transcribe mRNAs from it; usually
5880-409: 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
5978-404: The drug, and goes into complete remission in 70% of the cases within 6–10 months after discontinuing the drug. It is recommended that penicillamine be discontinued and thereafter avoided in patients who develop MG symptoms when treated with it. Botulinum toxin A : Botulinum toxin A (sold under the brand name Botox, Jeuveau, and Xeomin) blocks transmission at neuromuscular junctions to paralyze
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#17327906147576076-419: 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
6174-471: 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
6272-455: The eye lids), and other uncontrolled facial muscle spasms in MG patients without side effects or with only short-lived dysphagia or diplopia . Botulinum toxin A treatment, it is suggested, is best avoided in MG patients but may be offered with caution to patients with mild or stable MG using gradual increases in its dosages and close monitoring. Magnesium : Magnesium is a chemical element that blocks skeletal muscle contraction by inhibiting
6370-404: 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
6468-496: The first line immunosuppressive treatment for MG. To avoid exacerbation of MG, it is recommended that the corticosteroids should be started at a low dose and gradually increased to the dose achieving maximal responses. To achieve a faster therapeutic responses in cases with severe MG symptoms, it has been recommended to start with high doses of oral or intravenous glucocorticoids after first treating patients with plasmapheresis or intravenous immunoglobulin therapy, each of which reduces
6566-426: The first years of childhood, although they may not be recognized until adulthood. When diagnosed with MG, patient can be stratified into distinct subgroups based on the clinical features and serological status, e.g. affected muscle group, age of onset, thymic abnormalities, and profile of serum autoantibodies. Based on the affected muscle group, patients can be sub-grouped into ocular MG or generalized MG. Ocular MG
6664-471: The forehead muscles to compensate for the weakness in the eyelids. The clinical examiner might also try to elicit the "curtain sign" in a person by holding one of the person's eyes open, which in the case of MG will lead the other eye to close. If the diagnosis is suspected, serology can be performed: Muscle fibers of people with MG are easily fatigued, which the repetitive nerve stimulation test can help diagnose. In single-fiber electromyography , which
6762-435: 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
6860-412: 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
6958-476: The host genome. The DNA found is linear and the length of the genome. The genome encodes the usual retroviral genes pol, gag, and env as well as two additional genes tas or bel-1 and bet. The role for bet is not quite clear, research has shown that it is dispensable for replication of the virus in tissue culture. Recently, a novel mechanism was reported where foamy virus accessory protein Bet (unlike HIV-1 Vif) impaired
7056-496: 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
7154-430: 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
7252-513: 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
7350-405: The mother remains asymptomatic . MG can be difficult to diagnose, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders. Three types of myasthenic symptoms in children can be distinguished: Congenital myasthenias cause muscle weakness and fatigability similar to those of MG. The signs of congenital myasthenia usually are present in
7448-406: The mouth closed (the "hanging jaw sign") and as a snarling expression when attempting to smile. With drooping eyelids, facial weakness may make the individual appear sleepy or sad. Difficulty in holding the head upright may occur. The muscles that control breathing and limb movements can also be affected; rarely do these present as the first symptoms of MG, but develop over months to years. In
7546-428: The muscles into which it is injected. Local botulinum toxin A injections for cosmetic purposes have on occasion caused weaknesses in distant muscles, symptoms resembling ocular or generalized MG in individuals with subclinical MG, and exacerbations of previously controlled MG. Botulinum toxin A has also been used to treat spasmodic torticollis (i.e., involuntarily neck turning), blepharospasm (involuntary contraction of
7644-424: 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
7742-537: 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
7840-437: 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
7938-521: The rare cases where the statin caused the development or worsening of MG. Ia antiarrhythmic agents : A type Ia antiarrhythmic agent (see Vaughan Williams classification ), i.e., procainamide , which is used to treat cardiac arrhythmias , has caused respiratory failure in MG patients who, prior to being treated with it, did not have respiratory symptoms. Furthermore, this drug has caused MG-like symptoms in patients who have kidney failure but do not have MG. And, procainamide worsened muscle dysfunction in
8036-675: The rarity or absent reports on their exacerbation of MG, the following antibiotics are considered safe to use in MG patients: the cephalosporin class of drugs, sulfa drugs , the tetracycline group of drugs , clindamycin , polymyxin B , and nitrofurantoin . Immune checkpoint inhibitors : Immune checkpoint inhibitors promote certain types of autoimmune responses by blocking checkpoint pathways that inhibit these responses. They are used to treat cancers that promote their own growth and spread by stimulating checkpoint pathways. These checkpoint inhibitors include pembrolizumab , nivolumab , ipilimumab , avelumab , atezolizumab , and durvalumab . From
8134-625: The release or acetylcholine at the neuromuscular junction and also by lowering the sensitivity of these muscles to acetylcholine. Respiratory failure has occurred after systemic use of magnesium (mainly in the form of intravenous magnesium sulfate injections) for pre-eclampsia and after magnesium replacement during the course of a hospitalization in patients with underlying MG. It is suggested that magnesium when given intravenously or when given orally at high doses should be used with extreme caution in MG patients. Local anesthetics : Local anesthetics cause absence of pain and all other sensations in
8232-483: 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
8330-470: The thymus gland is large and abnormal. It sometimes contains clusters of immune cells that indicate lymphoid hyperplasia, and the thymus gland may give wrong instructions to immune cells. For women who are pregnant and already have MG, in a third of cases, they have been known to experience an exacerbation of their symptoms, and in those cases, it usually occurs in the first trimester of pregnancy. Signs and symptoms in pregnant mothers tend to improve during
8428-783: 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
8526-497: The two genomes shared 89–92% of their nucleotides and 95–97% of the amino acids are identical between the human virus and various SFV strains. These results indicated that SFVcpz(hu) is likely a variant of SFV and not a unique isolate. When looking at the origin of the human FV, sequence comparisons showed that from four different species of chimpanzees, SFVcpz(hu) was most closely related to the Eastern chimpanzee . This subspecies has
8624-469: The use of succinylcholine in MG (and other neuromuscular disorders) should probably be avoided where feasible. Inhalation anesthetics : Inhalation anesthetics are general anesthetics that are delivered by inhalation generally for patients undergoing surgery. MG patients undergoing surgery with inhaled anesthetics (i.e., halothane , isoflurane , enflurane , and sevoflurane ) may develop neuromuscular blockage and have an increased incidence of developing
8722-405: 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
8820-486: 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
8918-424: 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 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
9016-478: The virus’ etiological role is still unclear. Recent studies indicate that it is not pathogenic in humans and experimentally infected animals. If, in fact, HFV is not pathogenic in humans and is a retrovirus , it is an ideal vector for gene therapy. Another important feature of the virus is that the Gag, Pol, and Env proteins are synthesized independently; this is important because it means that each protein can be provided in trans on three different plasmids to create
9114-511: The weakness and fatigue are worse toward the end of the day. MG generally starts with ocular (eye) weakness; it might then progress to a more severe generalized form, characterized by weakness in the extremities or in muscles that govern basic life functions. In about two-thirds of individuals, the initial symptom of MG is related to the muscles around the eye. Eyelid drooping ( ptosis may occur due to weakness of m. levator palpebrae superioris ) and double vision ( diplopia , due to weakness of
9212-415: The worsening of MG symptoms. Penicillamine : Penicillamine is a chelation therapy drug used to treat various diseases (e.g., Wilson's disease ). About 1-2% of individuals treated long term with penicillamine develop MG and/or develop low concentrations of antibodies to AChR. Their MG is often mild and predominantly ocular MG, becomes evident usually 6–7 months (range one month to 8 years) after starting
9310-549: 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
9408-428: Was demonstrable, the phenotype having features comparable to congenital myasthenic syndromes and channelopathies . Signs and symptoms of myasthenia presenting from infancy or childhood may be one of the congenital myasthenic syndromes , which can be inherited in either an autosomal dominant or recessive manner. There are currently over two dozen types of congenital myasthenic syndromes. Limb–girdle myasthenia gravis
9506-422: Was in 1954. It was found as a contaminant in primary monkey kidney cultures. The first isolate of the “foamy viral agent” was in 1955. Not too long after this, it was isolated from a wide variety of New and Old World monkeys , cats, and cows. It was not until several years later that humans entered the scene. In 1971, a viral agent with FV-like characteristics was isolated from lymphoblastoid cells released from
9604-411: Was no follow-up data for 54 patients. Among these cases, 56% were considered to be serious. Non-statin cholesterol-lowering drugs, (e.g., niacin and the bile acid sequestrants drugs cholestyramine , colestipol , colesevelam , alirocumab , and evolocumab ) have been used in patients without causing or worsening MG. It is advised that a statin be discontinued and thereafter all statins be avoided in
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