GB virus C

GB virus C (GBV-C), formerly known as hepatitis G virus (HGV) and also known as human pegivirus – HPgV is a virus in the family Flaviviridae and a member of the Pegivirus,[1] is known to infect humans, but is not known to cause human disease. Reportedly, HIV patients coinfected with GBV-C can survive longer than those without GBV-C, but the patients may be different in other ways. Research is active into the virus' effects on the immune system in patients coinfected with GBV-C and HIV.[2][3][4]

Pegivirus C
Virus classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Kitrinoviricota
Class: Flasuviricetes
Order: Amarillovirales
Family: Flaviviridae
Genus: Pegivirus
Species:
Pegivirus C

Human infection

The majority of immunocompetent individuals clear GBV-C viraemia, but in some individuals, infection persists for decades.[5] However, the time interval between GBV-C infection and clearance of viraemia (detection of GBV-C RNA in plasma) is not known.

About 2% of healthy US blood donors are viraemic with GBV-C, and up to 13% of blood donors have antibodies to E2 protein, indicating possible prior infection.[5]

Parenteral, sexual, and vertical transmissions of GBV-C have been documented. Because of shared modes of transmission, individuals infected with HIV are often coinfected with GBV-C; the prevalence of GBV-C viraemia in HIV patients ranges from 14 to 43%.[6]

Several but not all studies have suggested that coinfection with GBV-C slows the progression of HIV disease.[7] In vitro models also demonstrated that GBV-C slows HIV replication. This beneficial effect may be related to action of several GBV-C viral proteins, including NS5A phosphoprotein and E2 envelope protein.[8]

Virology

It has a single-stranded, positive-sense RNA genome of about 9.3 kb and contains a single open reading frame (ORF) encoding two structural (E1 and E2) and five nonstructural (NS2, NS3, NS4, NS5A, and NS5B) proteins. GB-C virus does not appear to encode a C (core or nucleocapsid) protein like, for instance, hepatitis C virus. Nevertheless, viral particles have been found to have a nucleocapsid. The source of the nucleocapsid protein remains unknown.[1]

Taxonomy

GBV-C is a member of the family Flaviviridae and is phylogenetically related to hepatitis C virus, but replicates 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 Flaviviridae 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] GBV-D may be ancestral to GBV-A and GBV-C.[13]

The mutation rate of the GBV-C genome has been estimated at 10−2 to 10−3 substitutions/site/year.[14]

Epidemiology

GBV-C infection has been found worldwide and currently infects around a sixth of the world's population. 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. About 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 seven genotypes and many subtypes with distinct geographical distributions.[15] Genotypes 1 and 2 are prevalent in Northern and Central Africa and in Americas. Genotypes 3 and 4 are commons in Asia. Genotype 5 is present in Central and Southern Africa. Genotype 6 can be encountered in Southeast Asia. Finally, genotype 7 has been reported in China. Infection with multiple genotypes is possible.[16]

Genotype 5 appears to be basal in the phylogenetic tree, suggesting an African origin for this virus.[17]

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.[18][19][20][21] 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.[22] GB Virus C (and indeed, GBV-A and GBV-B) is named after the surgeon, G. Barker, who 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.[23]

References
  1. Stapleton, J. T.; Foung, S.; Muerhoff, A. S.; Bukh, J.; Simmonds, P. (2010). "The GB viruses: A review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae". Journal of General Virology. 92 (2): 233–46. doi:10.1099/vir.0.027490-0. PMC 3081076. PMID 21084497.
  2. Xiang J, George SL, Wünschmann S, et al. (2004). "Inhibition of HIV-1 replication by GB virus C infection through increases in RANTES, MIP-1alpha, MIP-1beta, and SDF-1". Lancet. 363 (9426): 2040–6. doi:10.1016/S0140-6736(04)16453-2. PMID 15207954. S2CID 54317667.
  3. 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. S2CID 19630054.
  4. 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. S2CID 45809720.
  5. "Hepatitis G". My Health and Nutrition. Archived from the original on 2013-11-02.
  6. 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.
  7. 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.
  8. Giret, M. T. M.; Kallas, E. G. (March 2012). "GBV-C: State of the Art and Future Prospects". Current HIV/AIDS Reports. 9 (1): 26–33. doi:10.1007/s11904-011-0109-1. PMID 22246585. S2CID 22887740.
  9. 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. S2CID 28977057.
  10. 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.
  11. 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. doi:10.1128/JVI.70.9.6126-6135.1996. PMC 190635. PMID 8709237.
  12. 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.
  13. 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 (7): e1000972. doi:10.1371/journal.ppat.1000972. PMC 2895649. PMID 20617167.
  14. Romano CM, Zanotto PM, Holmes EC (March 2008). "Bayesian coalescent analysis reveals a high rate of molecular evolution in GB virus C". J. Mol. Evol. 66 (3): 292–7. Bibcode:2008JMolE..66..292R. doi:10.1007/s00239-008-9087-3. PMC 3324782. PMID 18320258.
  15. Feng Y, Zhao W, Feng Y, Dai J, Li Z, Zhang X, Liu L, Bai J, Zhang H, Lu L, Xia X (2011). Davis T (ed.). "A Novel Genotype of GB Virus C: Its Identification and Predominance among Injecting Drug Users in Yunnan, China". PLOS ONE. 6 (10): e21151. Bibcode:2011PLoSO...621151F. doi:10.1371/journal.pone.0021151. PMC 3188531. PMID 21998624.
  16. Singh, Shivank; Blackard, Jason T (2017). "Human pegivirus (HPgV) infection in sub-Saharan Africa-A call for a renewed research agenda". Reviews in Medical Virology. 27 (6): e1951. doi:10.1002/rmv.1951. PMID 29148108. S2CID 4061848.
  17. Muerhoff AS, Leary TP, Sathar MA, Dawson GJ, Desai SM (June 2005). "African origin of GB virus C determined by phylogenetic analysis of a complete genotype 5 genome from South Africa". J. Gen. Virol. 86 (Pt 6): 1729–35. doi:10.1099/vir.0.80854-0. PMID 15914851.
  18. 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. Bibcode:1995PNAS...92.3401S. doi:10.1073/pnas.92.8.3401. PMC 42174. PMID 7724574.
  19. 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. S2CID 27358642.
  20. 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. S2CID 42480382.
  21. 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. S2CID 38749195.
  22. 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.
  23. Reshetnyak, VI; Karlovich, TI; Ilchenko, LU (2008). "Hepatitis G virus". World Journal of Gastroenterology. 14 (30): 4725–34. doi:10.3748/wjg.14.4725. PMC 2739332. PMID 18720531.
  • GBV-C at the US National Library of Medicine Medical Subject Headings (MeSH)
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