Hepatitis C virus surveillance and identification of human pegivirus 2 in a large Cameroonian cohort

Rodgers, Mary A.; Holzmayer, Vera; Vallari, Ana; Olivo, Ana; Forberg, Kenn; Fuhrman, Jill; Coller, Kelly E.; Awazi, Bih; Sidje, Jules Bertrand Kenmegne; Frankel, Matthew; Berg, Michael G.; Mbanya, Dora; Ndembi, Nicaise; Cloherty, Gavin

doi:10.1111/jvh.12996

Cited by 14 publications

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“…HPgV, formerly called hepatitis G virus (HGV) [9] or GB virus type C (GBV-C) [1], and the second human pegivirus (HPgV-2) [10] or human hepegivirus-1 (HHpgV-1) [5]. HPgV-2 was first reported in the US in 2015 [5,10], and has since been documented in the UK, China, Vietnam, Cameroon, and Iran [11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies revealed a low prevalence of HPgV-2 viremia in the general population, and an increased prevalence in patients infected with hepatitis C virus (HCV) [10,12,13,15] as well as in people who inject drugs (PWID) and are co-infected with HCV and human immunodeficiency virus type one (HIV-1) [11,15,25,26]. These data show a strong association between HPgV-2 and HCV and especially HCV/ HIV-1 co-infection [10-13, 15, 25, 26].…”

Section: Introductionmentioning

confidence: 99%

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Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication

Wan

Liu

et al. 2020

Emerging Microbes & Infections

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Tang (2020) Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication, Emerging Microbes & Infections, 9:1,[485][486][487][488][489][490][491][492][493][494][495] ABSTRACT The second human pegivirus HPgV-2 is a novel blood-borne virus that is strongly associated with the hepatitis C virus (HCV) infection. However, the molecular evidence for their association as well as the natural history and tissue tropism of HPgV-2 remain to be elucidated. In this longitudinal study, a total of 753 patients including 512 HIV-1 and HCV coinfected patients were enrolled to characterize the natural history of HPgV-2 infection. Peripheral blood mononuclear cells (PBMCs) and liver biopsies were collected to determine the tissue tropism of HPgV-2 using immunohistochemical staining of the HPgV-2 antigen and in situ hybridization of HPgV-2 RNA. We documented both persistent HPgV-2 infection with the presence of HPgV-2 viral RNA and antibodies up to 4.6 years and resolved HPgV-2 infection, accompanied by a simultaneous decline of anti-HPgV-2 antibodies and clearance of HPgV-2 viremia. Furthermore, we observed the clearance of HCV, but not HPgV-2, by treatment with direct-acting antivirals (DAAs). Biochemical tests and pathological analyses did not reveal any indication of hepatic impairment caused by HPgV-2. HPgV-2 RNA and nonstructural antigen were detected in the lymphocytes, but not in the hepatocytes present in the liver biopsy samples. In addition, both positive-and negative-strand HPgV-2 RNAs were detected in PBMCs, especially in B cells. The present study is the first to provide evidence that HPgV-2 is a lymphotropic, but not a hepatotropic virus and that HPgV-2 replication is independent of HCV viremia. These new findings let us gain insights into the evolution and persistent infection of RNA viruses in humans.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication

Wan

Liu

et al. 2020

Emerging Microbes & Infections

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“…Since then, HPgV-2 has been documented in the USA, UK, China, Vietnam, Cameroon, Iran, etc. (Bonsall et al, 2016;Anh et al, 2018;Bijvand et al, 2018;Wang et al, 2018a;Rodgers et al, 2019). It is noteworthy that HPgV-2 is epidemiologically tightly associated with HCV infection (Berg et al, 2015;Anh et al, 2018;Kandathil et al, 2018;Wang et al, 2018a;Wang et al, 2018b;Rodgers et al, 2019) and shares several common genomic features with HCV (Kapoor et al, 2015;Bonsall et al, 2016;Coller et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…(Bonsall et al, 2016;Anh et al, 2018;Bijvand et al, 2018;Wang et al, 2018a;Rodgers et al, 2019). It is noteworthy that HPgV-2 is epidemiologically tightly associated with HCV infection (Berg et al, 2015;Anh et al, 2018;Kandathil et al, 2018;Wang et al, 2018a;Wang et al, 2018b;Rodgers et al, 2019) and shares several common genomic features with HCV (Kapoor et al, 2015;Bonsall et al, 2016;Coller et al, 2016). HCV is a genetically diverse RNA virus and has seven genotypes and 67 subtypes (Smith et al, 2014) due to high error rate of RNA polymerase during replication (Moradpour et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…HCV is a genetically diverse RNA virus and has seven genotypes and 67 subtypes (Smith et al, 2014) due to high error rate of RNA polymerase during replication (Moradpour et al, 2007). In contrast, the overall nucleotide identity among HPgV-2 consensus sequences worldwide is about 94%, and no apparent hypervariable regions are observed within HPgV-2 genome (Berg et al, 2015;Wang et al, 2018b;Rodgers et al, 2019;Sridhar et al, 2019;Forberg et al, 2020). These results indicate the significant difference of HPgV-2 and HCV with respect to their interhost genetic diversity.…”

Section: Introductionmentioning

confidence: 99%

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Difference of Intrahost Dynamics of the Second Human Pegivirus and Hepatitis C Virus in HPgV-2/HCV-Coinfected Patients

Liang

Fan

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundThe second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significantly different genetic diversity. The comparison of intrahost dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their intrahost difference of genetic diversity and the possible mechanisms.MethodsIntrahost single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross-sectional and longitudinal samples from HPgV-2- and HCV-coinfected patients. The levels of human cytokines were quantified in the patient before and after HCV elimination by the treatment of direct-acting antivirals (DAA).ResultsUnlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2-infected patients. However, iSNV analysis confirmed the intrahost variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intrahost variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying or negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since proinflammatory cytokine expression dramatically decreased with elimination of HCV.ConclusionThis study provided new insights into the intrahost genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The different genetic diversity of HPgV-2 and HCV makes HPgV-2 a potential new model to investigate RNA virus diversity and the mechanism of viral polymerase in modulating virus replication.

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Spatiotemporal Phylodynamics of Hepatitis C Among People Who Inject Drugs in India

Clipman¹,

Mehta²,

Rodgers

et al. 2021

Hepatology

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Hepatitis C virus surveillance and identification of human pegivirus 2 in a large Cameroonian cohort

Cited by 14 publications

References 38 publications

Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication

Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication

Difference of Intrahost Dynamics of the Second Human Pegivirus and Hepatitis C Virus in HPgV-2/HCV-Coinfected Patients

Spatiotemporal Phylodynamics of Hepatitis C Among People Who Inject Drugs in India

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