GB virus C
GB virus C (GBV-C), formerly known as hepatitis G virus (HGV), is a virus in the Flaviviridae family which has not yet been assigned to a genus, is known to infect humans, but is not known to cause human disease. There have been reports that HIV patients coinfected with GBV-C can survive longer than those without GBV-C, but the patients may be different in other ways. There is current active research into the virus' effects on the immune system in patients coinfected with GBV-C and HIV.[1][2]
History
Hepatitis G virus and GB virus C (GBV-C) are RNA viruses that were independently identified in 1995, and were subsequently found to be two isolates of the same virus.[3][4][5][6] Although GBV-C was initially thought to be associated with chronic hepatitis, extensive investigation failed to identify any association between this virus and any clinical illness.[7] GB Virus C is named after the surgeon, G. Barker, who first fell ill in 1966 with a non-A non-B hepatitis which at the time was thought to have been caused by a new, infectious hepatic virus.[8]
Taxonomy
GBV-C is a member of the Flaviviridae family and is phylogenetically related to hepatitis C virus but appears to replicate primarily in lymphocytes, and poorly if at all in hepatocytes.[9][10] GBV-A and GBV-B are probably tamarin viruses, while GBV-C infects humans.[11] The GB viruses have been tentatively assigned to a fourth genus within the Flavivirdae named "Pegivirus", but this has yet to be formally endorsed by The International Committee on Taxonomy of Viruses.[12]
Another member of this clade GBV-D has been isolated from a bat (Pteropus giganteus).[13] It appears that GBV-D is ancestral to GBV-A and GBV-C.
The mutation rate of the genome has been estimated at 10-2 to 10-3 substitutions/site/year.[14]
Epidemiology
GBV-C infection has been found worldwide. High prevalence is observed among subjects with the risk of parenteral exposures including those with exposure to blood and blood products, those on hemodialysis, and intravenous drug users. Sexual contact and vertical transmission may occur. ~10–25% of hepatitis C infected patients and 14–36% of drug users who are seropositive for HIV-1 show the evidence of GBV-C infection.
It has been classified into six genotypes and many subtypes with distinct geographical distributions. A seventh has also been described.[15]
Genotype 1 is predominant in Africa and is divided into five subtypes. Genotype 2 has three subtypes and is found in Europe and America. Genotype 3 is the most common in Asia including Japan and China. Genotype 4 is predominant in Southeast Asia and genotype 5 is only seen in South Africa. Genotype 6 has been described in Indonesia.
Virology
It has a single stranded positive RNA genome of about 9.3 kb and contains a single open reading frame (ORF) encoding two structural (E1 and E2) and five non-structural (NS2, NS3, NS4, NS5A, and NS5B) proteins.
Human infection
The majority of immune-competent individuals appear to clear GBV-C viraemia within the first few years following infection and although the time interval between GBV-C infection and clearance of viraemia (detection of GBV-C RNA in plasma) is not known, infection may persist for decades in some individuals.
Approximately 2% of healthy US blood donors are viraemic with GBV-C, and up to 13% of blood donors have antibodies to E2 protein, indicating prior infection.
Parenteral, sexual and vertical transmission of GBV-C have all been documented, and because of shared modes of transmission, individuals infected with HIV are commonly co-infected with GBV-C. Among people with HIV infection, the prevalence of GBV-C viraemia ranges from 14 to 43%.[16]
Some studies have suggested that co-infection with GBV-C will actually slow the progression of HIV disease.[17]
References
- ^ Mosam A, Sathar MA, Dawood H, Cassol E, Esterhuizen TM, Coovadia HM (2007). "Effect of GB Virus C Co-infection on Response to Generic HAART in African Patients with HIV-1 Clade C Infection". AIDS 21 (10): 1377–9. doi:10.1097/QAD.0b013e3281532cb8. PMID 17545721.
- ^ Jung S, Eichenmüller M, Donhauser N, et al. (2007). "HIV Entry Inhibition by the Envelope 2 Glycoprotein of GB Virus C". AIDS 21 (5): 645–7. doi:10.1097/QAD.0b013e32803277c7. PMID 17314528.
- ^ Simons JN, Pilot-Matias TJ, Leary TP, et al. (April 1995). "Identification of two flavivirus-like genomes in the GB hepatitis agent". Proc. Natl. Acad. Sci. USA 92 (8): 3401–5. doi:10.1073/pnas.92.8.3401. PMC 42174. PMID 7724574. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=42174.
- ^ Simons JN, Leary TP, Dawson GJ, et al. (June 1995). "Isolation of Novel Virus-like Sequences Associated with Human Hepatitis". Nat. Med. 1 (6): 564–9. doi:10.1038/nm0695-564. PMID 7585124.
- ^ Yoshiba M, Okamoto H, Mishiro S (October 1995). "Detection of the GBV-C Hepatitis Virus Genome in Serum from Patients with Fulminant Hepatitis of Unknown Aetiology". Lancet 346 (8983): 1131–2. doi:10.1016/S0140-6736(95)91802-7. PMID 7475605.
- ^ Birkenmeyer LG, Desai SM, Muerhoff AS, Leary TP, Simons JN, Montes CC, Mushahwar IK (1998). "Isolation of a GB Virus-related Genome from a Chimpanzee". J. Med. Virol. 56 (1): 44–51. doi:10.1002/(SICI)1096-9071(199809)56:1<44::AID-JMV8>3.0.CO;2-N. PMID 9700632.
- ^ Alter, H. J. (June 1996). "The Cloning and Clinical Implications of HGV and HGBV-C". N. Engl. J. Med. 334 (23): 1536–7. doi:10.1056/NEJM199606063342310. PMID 8618611. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=8618611&promo=ONFLNS19.
- ^ Reshetnyak, VI; Karlovich, TI; Ilchenko, LU (2008). "Hepatitis G virus". World journal of gastroenterology : WJG 14 (30): 4725–34. doi:10.3748/wjg.14.4725. PMC 2739332. PMID 18720531. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2739332.
- ^ Leary TP, Muerhoff AS, Simons JN, Pilot-Matias TJ, Erker JC, Chalmers ML, Schlauder GG, Dawson GJ, Desai SM, Mushahwar IK (1996). "Sequence and Genomic Organization of GBV-C: A Novel Member of the Flaviviridae Associated with Human Non-A–E Hepatitis". J. Med. Virol. 48 (1): 60–7. doi:10.1002/(SICI)1096-9071(199601)48:1<60::AID-JMV10>3.0.CO;2-A. PMID 8825712.
- ^ Thurner C, Witwer C, Hofacker IL, Stadler PF (May 2004). "Conserved RNA Secondary Structures in Flaviviridae Genomes". J. Gen. Virol. 85 (Pt 5): 1113–24. doi:10.1099/vir.0.19462-0. PMID 15105528. http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=15105528.
- ^ Simons JN, Desai SM, Schultz DE, Lemon SM, Mushahwar IK (1996). "Translation initiation in GB viruses A and C: evidence for internal ribosome entry and implications for genome organization". J. Virol. 70 (9): 6126–35. PMC 190635. PMID 8709237. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=190635.
- ^ Stapleton JT, Foung S, Muerhoff AS, Bukh J, Simmonds P (February 2011). "The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae". The Journal of General Virology 92 (Pt 2): 233–46. doi:10.1099/vir.0.027490-0. PMC 3081076. PMID 21084497. http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=21084497.
- ^ Epstein JH, Quan PL, Briese T, et al. (2010). "Identification of GBV-D, a novel GB-like flavivirus from old world frugivorous bats (Pteropus giganteus) in Bangladesh". PLoS Pathog. 6: e1000972. doi:10.1371/journal.ppat.1000972. PMC 2895649. PMID 20617167. http://dx.plos.org/10.1371/journal.ppat.1000972.
- ^ Romano CM, Zanotto PM, Holmes EC (2008) Bayesian coalescent analysis reveals a high rate of molecular evolution in GB virus C. J Mol Evol 66(3):292-297
- ^ Feng Y, Zhao W, Feng Y, Dai J, Li Z, Zhang X, Liu L, Bai J, Zhang H, Lu L, Xia X (2011). Davis, Todd. ed. "A Novel Genotype of GB Virus C: Its Identification and Predominance among Injecting Drug Users in Yunnan, China". PLoS One 6 (10): e21151. doi:10.1371/journal.pone.0021151. PMC 3188531. PMID 21998624. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0021151.
- ^ George SL, Varmaz D, Stapleton JT (2006). "GB Virus C Replicates in Primary T and B Lymphocytes". J. Infect. Dis. 193 (3): 451–4. doi:10.1086/499435. PMID 16388494.
- ^ Zhang W, Chaloner K, Tillmann HL, Williams CF, Stapleton JT (2006). "Effect of Early and Late GB Virus C Viraemia on Survival of HIV-infected Individuals: A Meta-analysis". HIV Med. 7 (3): 173–180. doi:10.1111/j.1468-1293.2006.00366.x. PMID 16494631. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1464-2662&date=2006&volume=7&issue=3&spage=173.
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