Clinical and epidemiological significance of pegivirus (virus hepatitis G) in patients with HIV infection and other infectious and non-infectious diseases
https://doi.org/10.22625/2072-6732-2025-17-3-13-23
Abstract
Purpose – to analyse current scientific data on Human pegivirus type 1 (HPgV-1) infection. The review examines virus structure, epidemiology, transmission routes, pathogenesis features, impact on various human diseases, modern diagnostic methods, and therapeutic approaches for HPgV infection. A search of scientific publications was conducted in PubMed, Elibrary, CyberLeninka, and Scopus using keywords «Human pegivirus», «HPgV», «GBV-C», «Hepatitis G virus» for 1990-November 2024. Inclusion criteria were original research articles, reviews, and meta-analyses on HPgV-1 in Russian and English. Article selection was two-staged: initial screening by titles and abstracts, then full-text analysis of articles meeting criteria.
HPgV-1 is a lymphotropic RNA virus of the Flaviviridae family, globally distributed with an overall infection prevalence of approximately 3,1%, varying regionally. Main transmission routes are parenteral, vertical, and sexual. Diagnostic methods are PCR and ELISA. No specific antiviral treatment is currently developed. A significant clinical aspect is HPgV-1’s modulating effect on HIV infection, slowing disease progression and increasing CD4+ lymphocyte counts. A possible association with increased risk of non-Hodgkin’s lymphoma and neuroinfections is discussed, but these data need further confirmation.
Conclusion: HPgV-1 infection is a significant public health and biomedical research problem due to its wide prevalence and potential impact on various diseases, especially HIV. The protective effect of HPgV-1 against HIV offers new perspectives for therapeutic strategies. Further in-depth studies are needed to understand HPgV-1 pathogenesis mechanisms and clinical role in various pathologies.
About the Authors
D. A. PimenovRussian Federation
Nizhny Novgorod
Competing Interests:
None
D. A. Nechayeva
Russian Federation
Nizhny Novgorod
Competing Interests:
None
O. L. Sobolevskaya
Russian Federation
Nizhny Novgorod
Competing Interests:
None
V. V. Krasnov
Russian Federation
Nizhny Novgorod
Competing Interests:
None
E. A. Levina
Russian Federation
Nizhny Novgorod
Competing Interests:
None
References
1. Stapleton J.T., Foung S., Muerhoff A.S., et al. 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. 2011; 92(2): 233–246. DOI: 10.1099/vir.0.027490-0.
2. Smith D.B., Becher P., Bukh J., et al. Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family. Journal of General Virology. 2016; 97(11): 2894–2907. DOI: 10.1099/jgv.0.000612.
3. Adams M.J., King A.M.Q., Carstens E.B. Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2013). Archives of Virology. 2013; 158(9): 2023–2030. DOI: 10.1007/s00705-013-1688-5.
4. Wang H., Wan Z., Xu R., et al. A Novel Human Pegivirus, HPgV-2 (HHpgV-1), Is Tightly Associated With Hepatitis C Virus (HCV) Infection and HCV/Human Immunodeficiency Virus Type 1 Coinfection. Clinical Infectious Diseases. 2018; 66(1): 29–35. DOI: 10.1093/cid/cix748.
5. Stapleton J.T. GB virus type C/Hepatitis G virus. Seminars in Liver Disease. 2003; 23(2): 137–148. DOI: 10.1055/s-2003-39943.
6. Marano G., Franchini M., Farina B. The human pegivirus: a new name for an “ancient” virus. Acta Virologica. 2017; 61(4): 401–412. DOI: 10.4149/av_2017_04_401.
7. Quan P.-L., Firth C., Conte J.M., et al. Bats are a major natural reservoir for hepaciviruses and pegiviruses. PNAS. 2013; 110(20): 8194–8199. DOI: 10.1073/pnas.1303037110.
8. Xiang J., Klinzman D., McLinden J., et al. Characterization of hepatitis G virus (GB-C Virus) particles: evidence for a nucleocapsid and expression of sequences upstream of the E1 protein. Journal of Virology. 1998; 72(4): 2738–2744. DOI: 10.1128/jvi.72.4.2738-2744.1998.
9. Chivero E.T., Bhattarai N., McLinden J.H., et al. Human Pegivirus (HPgV; formerly known as GBV-C) inhibits IL-12 dependent natural killer cell function. Virology. 2015; 485: 116–127. DOI: 10.1016/j.virol.2015.07.008.
10. Pessoa M.G., Terrault N.A., Detmer J., et al. Quantitation of hepatitis G and C viruses in the liver: evidence that hepatitis G virus is not hepatotropic. Hepatology. 1998; 27(3): 877–879. DOI: 10.1002/hep.510270331.
11. Yang N., Dai R., Zhang X. Global prevalence of human pegivirus-1 in healthy volunteer blood donors: a systematic review and meta-analysis. Vox Sanguinis. 2020; 115(2): 107–119. DOI: 10.1111/vox.12868.
12. Reshetnyak V.I., Karlovich T.I., Ilchenko L.U. Hepatitis G virus. World Journal of Gastroenterology. 2008; 14(30): 4725–4734. DOI: 10.3748/wjg.14.4725.
13. Chivero E.T., Bhattarai N., Rydze R.T., et al. Human pegivirus RNA is found in multiple blood mononuclear cells in vivo and serumderived viral RNA-containing particles are infectious in vitro. Journal of General Virology. 2014; 95(6): 1307–1319. DOI: 10.1099/vir.0.063016-0.
14. Chen S., Wang H., Dzakah E.E., et al. The Second Human Pegivirus, a Non-Pathogenic RNA Virus with Low Prevalence and Minimal Genetic Diversity. Viruses. 2022; 14(9): 1844. DOI: 10.3390/v14091844.
15. Toyoda H., Takahashi I., Fukuda Y., Hayakawa T., Takamatsu J. Comparison of Characteristics Between Patients With GB Virus C/Hepatitis G Virus (GBV-C/HGV) RNA and Those With GBV-C/HGV E2-Antibody in Patients With Hemophilia. Journal of Medical Virology. 2000; 60(1): 34–38. DOI: 10.1002/(sici)1096-9071(200001)60:1<34::aid-jmv6>3.0.co;2-k.
16. Stapleton J.T., Xiang J., McLinden J.H. A novel T cell evasion mechanism in persistent RNA virus infection. Transactions of the American Clinical and Climatological Association. 2014; 125: 14–24.
17. Agnello V., Abel G., Elfahal M., et al. Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor. PNAS. 1999; 96(22): 12766–12771. DOI: 10.1073/pnas.96.22.12766.
18. Wünschmann S., Muller H.M., Stipp C.S., et al. In Vitro Interaction between Hepatitis C Virus (HCV) Envelope Glycoprotein E2 and Serum Lipoproteins (LPs) Results in Enhanced Cellular Binding of Both HCV E2 and LPs. The Journal of Infectious Diseases. 2006; 194(8): 1058–1067. DOI: 10.1086/507647.
19. Lanteri M.C., Vahidnia F., Tan S., et al. Downregulation of Cytokines and Chemokines by GB Virus C After Transmission Via Blood Transfusion in HIV-Positive Blood Recipients. The Journal of Infectious Diseases. 2015; 211(10): 1585–1596. DOI: 10.1093/infdis/jiu660.
20. Fama A., Larson M.C., Link B.K., et al. Human Pegivirus Infection and Lymphoma Risk: A Systematic Review and Meta-analysis. Clinical Infectious Diseases. 2020; 71(5): 1221–1228. DOI: 10.1093/cid/ciz940.
21. Bhattarai N., Stapleton J.T. GB virus C: the good boy virus? Trends in Microbiology. 2012; 20(3): 124–130. DOI: 10.1016/j.tim.2012.01.004.
22. Podymova S.D. Parenteral’nye ostrye virusnye gepatity: sovremennaya diagnostika, profilaktika i lechenie. Eksperimental’naya i klinicheskaya gastroenterologiya. 2012; 6: 3–10. (In Russian).
23. Samadi M., Salimi V., Haghshenas M.R., et al. Clinical and molecular aspects of human pegiviruses in the interaction host and infectious agent. Virology Journal. 2022; 19(1): 41. DOI: 10.1186/s12985-022-01769-3.
24. Taklual W., Tang S., Yue W. Effect of human pegivirus route of transmission on the genetic distribution of the virus: an institution based cross-sectional study. Virology Journal. 2019; 16(1): 51. DOI: 10.1186/s12985-019-1161-5.
25. Zimmerman J., Blackard J.T. Human pegivirus type 1 infection in Asia—a review of the literature. Reviews in Medical Virology. 2022; 32(1): e2257. DOI: 10.1002/rmv.2257. Available at: https://doi.org/10.1002/rmv.2257 (Accessed 07.06.2024).
26. Singh S., Blackard J.T. Human pegivirus (HPgV) infection in sub-Saharan Africa-a call for a renewed research agenda. Reviews in Medical Virology. 2017; 27(6): e1951. DOI: 10.1002/rmv.1951.
27. Slavov S.N., Silveira R.M., Hespanhol M.R., et al. Human pegivirus-1 (HPgV-1) RNA prevalence and genotypes in volunteer blood donors from the Brazilian Amazon. Transfusion Clinique et Biologique. 2019; 26(4): 234–239. DOI: 10.1016/j.tracli.2019.06.005.
28. Alex D., Steve R.J., Ramalingam V.V., et al. Prevalence and potential impact of human pegivirus-1 on HIV-1 disease progression among Indian PLHIV. Journal of Infection in Developing Countries. 2024; 18(7): 1108–1117. DOI: 10.3855/jidc.19397.
29. Nguyen T.A., Nguyen T.T.H., Nhu L.N.T., et al. Detection and Characterization of Human Pegivirus 2, Vietnam. Emerging Infectious Diseases. 2018; 24(11): 2063–2067. DOI: 10.3201/eid2411.180668.
30. Rodgers M.A., Holzmayer V., Vallari A., et al. Hepatitis C virus surveillance and identification of human pegivirus 2 in a large Cameroonian cohort. Journal of Viral Hepatitis. 2019; 26(1): 30–37. DOI: 10.1111/jvh.12996.
31. Santos L.M., Lobato R.C., Barral M.F.M., et al. Prevalence and vertical transmission of human pegivirus among pregnant women infected with HIV. International Journal of Gynecology & Obstetrics. 2017; 138(1): 113–118. DOI: 10.1002/ijgo.12175.
32. Wejstal R., Manson A.S., Widell A., et al. Perinatal transmission of hepatitis G virus (GB virus type C) and hepatitis C virus infections--a comparison. Clinical Infectious Diseases. 1999; 28(4): 816–821. DOI: 10.1086/515187.
33. Jarvis L.M., Davidson F., Hanley J.P., et al. Infection with hepatitis G virus among recipients of plasma products. The Lancet. 1996; 348(9038): 1352–1355. DOI: 10.1016/s0140-6736(96)04041-x.
34. Seifried C., Weber M., Bialleck H., et al. High prevalence of GBV-C/HGV among relatives of GBV-C/HGV-positive blood donors in blood recipients and in patients with aplastic anemia. Transfusion. 2004; 44(2): 268–274. DOI: 10.1111/j.1537-2995.2004.00646.x.
35. Fabrizi F., Lunghi G., Bacchini G. Hepatitis G virus infection in chronic dialysis patients and kidney transplant recipients. Nephrology Dialysis Transplantation. 1997; 12(8): 1645–1651. DOI: 10.1093/ndt/12.8.1645.
36. Miao Z., Gao L., Song Y., et al. Prevalence and Clinical Impact of Human Pegivirus-1 Infection in HIV-1-Infected Individuals in Yunnan, China. Viruses. 2017; 9(2): 28. DOI: 10.3390/v9020028.
37. Frey S.E., Musial C.E., Homan S.M. Evidence for probable sexual transmission of the hepatitis G virus. Clinical Infectious Diseases. 2002; 34(8): 1033–1038. DOI: 10.1086/339551.
38. Leyssen P., De Clercq E., Neyts J. Perspectives for the treatment of infections with flaviviridae. Clinical Microbiology Reviews. 2000; 13(1): 67–82. DOI: 10.1128/CMR.13.1.67.
39. Zhu N., Xu R., Tang W., et al. Detection of a novel human pegivirus HPgV-2 in healthy blood donors and recipients of multiple transfusions: implications for blood safety. Chinese Journal of Blood Transfusion. 2018; 38(7): 842–849. DOI: 10.3969/j.issn.1673-4254.2018.07.12.
40. Li T., Tang S., Su Y., et al. High prevalence and viremia of human pegivirus 2 in the HIV-infected population in Honghe Prefecture, Yunnan Province. Archives of Virology. 2020; 165(3): 619–626. DOI: 10.1007/s00705-019-04512-6.
41. da Silva A.S., de Campos G.M., da Silva A.C.R., et al. Human Pegivirus-1 Detection and Genotyping in Brazilian Patients with Fulminant Hepatitis. Pathogens. 2023; 12(9): 1122. DOI: 10.3390/pathogens12091122.
42. Kanda T., Yokosuka O., Ehata T. Detection of GBV-C RNA in patients with non-A-E fulminant hepatitis by reverse-transcription polymerase chain reaction. Hepatology. 1997; 25(5): 1261–1265. DOI: 10.1002/hep.510250534.
43. Tuddenham R., Eden J.-S., Gilbey T. Human pegivirus in brain tissue of a patient with encephalitis. Diagnostic Microbiology and Infectious Disease. 2020; 96(2): 114898. DOI: 10.1016/j.diagmicrobio.2019.114898.
44. Balcom E.F., Doan M.A.L., Branton W.G., et al. Human pegivirus-1 associated leukoencephalitis: clinical and molecular features. Annals of Neurology. 2018; 84(5): 781–787. DOI: 10.1002/ana.25354.
45. Bukowska-Ośko I., Perlejewski K., Pawełczyk A., et al. Human pegivirus in patients with encephalitis of unclear etiology, Poland. Emerging Infectious Diseases. 2018; 24(10): 1929–1933. DOI: 10.3201/eid2410.171785.
46. Doan M.A.L., RoczkoSwsky A., Smith M., et al. Infection of glia by human pegivirus suppresses peroxisomal and antiviral signaling pathways. Journal of Virology. 2021; 95(22): e0107421. DOI: 10.1128/JVI.01074-21.
47. Lauck M., Bailey A.L., Andersen K.G., et al. GB virus C coinfections in West African Ebola patients. Journal of Virology. 2015; 89(4): 2425–2429. DOI: 10.1128/JVI.02821-14.
48. Zhang W., Chaloner K., Tillmann H.L., et al. Effect of early and late GB virus C viraemia on survival of HIV-infected individuals: a meta-analysis. HIV Medicine. 2006; 7(3): 173–180. DOI: 10.1111/j.1468-1293.2006.00366.x.
49. Moenkemeyer M., Stoll M., Tillmann H.L., et al. GBV-C coinfection is negatively correlated to Fas expression and Fasmediated apoptosis in HIV-1 infected patients. Journal of Medical Virology. 2008; 80(11): 1933–1940. DOI: 10.1002/jmv.21305.
50. Muerhoff A.S., Tillmann H.L., Manns M.P. GB virus C genotype determination in GB virus-C/HIV co-infected individuals. Journal of Medical Virology. 2003; 70(4): 631–638. DOI: 10.1002/jmv.10438.
51. Supapol W.B., Remis R.S., Chearskul S., et al. Reduced mother-tochild transmission of HIV associated with infant but not maternal GB virus C infection. The Journal of Infectious Diseases. 2008; 197(10): 1369–1377. DOI: 10.1086/587488.
52. Litvinov V.V., Freind G.G., Korobov V.P., Shestakova A.D. HPgV-infektsiya. Infektsionnye bolezni: Novosti. Mneniya. Obuchenie. 2021; 10(2(37)): 30–37 (In Russian, abstr. in English). DOI: 10.29296/24999490-2021-06-03.
53. George S.L., Varmaz D., Stapleton J.T. GB virus C replicates in primary T and B lymphocytes. The Journal of Infectious Diseases. 2006; 193(3): 451–454. DOI: 10.1086/499435.
Review
For citations:
Pimenov D.A., Nechayeva D.A., Sobolevskaya O.L., Krasnov V.V., Levina E.A. Clinical and epidemiological significance of pegivirus (virus hepatitis G) in patients with HIV infection and other infectious and non-infectious diseases. Journal Infectology. 2025;17(3):13-23. (In Russ.) https://doi.org/10.22625/2072-6732-2025-17-3-13-23