The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae

Stapleton, Jack T.; Foung, Steven K. H.; Muerhoff, A. Scott; Bukh, Jens; Simmonds, Peter

doi:10.1099/vir.0.027490-0

Cited by 254 publications

(360 citation statements)

References 125 publications

Supporting

Mentioning

327

Contrasting

Unclassified

Order By: Relevance

“…The human liver-chimeric mouse models and genetically engineered mice are useful for some studies, but lack functional immune systems or allow only limited viral replication (31). GBV-B infection of New World monkeys has been used as a surrogate model, but persistent infection is rare (12,31). Despite recent breakthroughs in HCV therapy (28), vaccine efforts lag far behind and would be aided by a better understanding of hepacivirus immunity and a preclinical model for testing vaccine candidate concepts (30,31).…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, hepaciviruses have also been discovered in rodents (6,9), bats (10), and Old World primates (11). Pegiviruses are closely related to hepaciviruses and include human (HPgV/ GBV-C) and simian (SPgV/GBV-A) pegiviruses, none of which are associated with disease (12). More recently, rodent (RPgV) (9), bat (BPgV) (10), and equine (EPgV and Theiler's disease associated virus, TDAV) (13,14) pegiviruses were discovered.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of nonprimate hepacivirus and construction of a functional molecular clone

Scheel

Kapoor

Nishiuchi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

133

View full text Add to dashboard Cite

Nonprimate hepacivirus (NPHV) is the closest known relative of hepatitis C virus (HCV) and its study could enrich our understanding of HCV evolution, immunity, and pathogenesis. High seropositivity is found in horses worldwide with ∼3% viremic. NPHV natural history and molecular virology remain largely unexplored, however. Here, we show that NPHV, like HCV, can cause persistent infection for over a decade, with high titers and negative strand RNA in the liver. NPHV is a near-universal contaminant of commercial horse sera for cell culture. The complete NPHV 3′-UTR was determined and consists of interspersed homopolymer tracts and an HCV-like 3′-terminal poly(U)-X-tail. NPHV translation is stimulated by miR-122 and the 3′-UTR and, similar to HCV, the NPHV NS3-4A protease can cleave mitochondrial antiviral-signaling protein to inactivate the retinoic acid-inducible gene I pathway. Using an NPHV consensus cDNA clone, replication was not observed in primary equine fetal liver cultures or after electroporation of selectable replicons. However, intrahepatic RNA inoculation of a horse initiated infection, yielding high RNA titers in the serum and liver. Delayed seroconversion, slightly elevated circulating liver enzymes and mild hepatitis was observed, followed by viral clearance. This establishes the molecular components of a functional NPHV genome. Thus, NPHV appears to resemble HCV not only in genome structure but also in its ability to establish chronic infection with delayed seroconversion and hepatitis. This NPHV infectious clone and resulting acute phase sera will facilitate more detailed studies on the natural history, pathogenesis, and immunity of this novel hepacivirus in its natural host.hepatitis C virus | infectious cDNA clone | equine liver disease | animal model | 3′-untranslated region

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Characterization of nonprimate hepacivirus and construction of a functional molecular clone

Scheel

Kapoor

Nishiuchi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

133

View full text Add to dashboard Cite

show abstract

“…Exosomes are microvesicles of endocytic origin that are emerging as novel particles employed by cells and viruses to transmit viral and cellular RNAs and proteins to cells (Meckes & Raab-Traub, 2011). As HPgV and other members of the genus Pegivirus do not appear to encode a nucleocapsid protein at the N terminus of the polyprotein (Xiang et al, 1998;Stapleton et al, 2011), cellular-derived microvesicles (which carry~50 % of the HPgV RNA found in plasma; Bhattarai et al, 2013) may be involved in virus release and/ or cellular infection. Supporting this hypothesis, HPgV RNA-containing microvesicles positive for an exosomal marker (cellular CD63) were able to deliver viral RNA to uninfected PBMCs and viral RNA replicated within these cells ex vivo (Chivero et al, 2014).…”

Section: Life Cyclementioning

confidence: 99%

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Chivero

Stapleton

2015

Journal of General Virology

View full text Add to dashboard Cite

Human pegivirus (HPgV; originally called GB virus C/hepatitis G virus) is an RNA virus within the genus Pegivirus of the family Flaviviridae that commonly causes persistent infection. Worldwide, 750 million people are actively infected (viraemic) and an estimated 0.75-1.5 billion people have evidence of prior HPgV infection. No causal association between HPgV and disease has been identified; however, several studies described a beneficial relationship between persistent HPgV infection and survival in individuals infected with human immunodeficiency virus. The beneficial effect appeared to be related to a reduction in host immune activation. HPgV replicates well in vivo (mean plasma viral loads typically .1¾10 7 genome copies ml -1 ); however, the virus grows poorly in vitro and systems to study this virus are limited. Consequently, mechanisms of viral persistence and host immune modulation remain poorly characterized, and the primary permissive cell type (s) has not yet been identified. HPgV RNA is found in liver, spleen, bone marrow and PBMCs, including Tand B-lymphocytes, NK-cells, and monocytes, although the mechanism of cell-to-cell transmission is unclear. HPgV RNA is also present in serum microvesicles with properties of exosomes. These microvesicles are able to transmit viral RNA to PBMCs in vitro, resulting in productive infection. This review summarizes existing data on HPgV cellular tropism and the effect of HPgV on immune activation in various PBMCs, and discusses how this may influence viral persistence. We conclude that an increased understanding of HPgV replication and immune modulation may provide insights into persistent RNA viral infection of humans. IntroductionHuman pegivirus (HPgV) is an RNA virus within the Pegivirus A species and family Flaviviridae (Adams et al., 2013;Stapleton et al., 2012a). The virus was originally called hepatitis G virus (HGV)/GB virus type C (GBV-C). The letters 'GB' represented the initials of a surgeon with acute hepatitis whose sera caused hepatitis in marmosets (Deinhardt et al., 1967). Subsequent studies found that this virus did not cause hepatitis and there was no direct evidence that the surgeon ('G. B.') was infected with HPgV. Thus, the virus (HGV/GBV-C), along with several related primate and bat viruses (GBV-A, GBV-C czp , GBV-D), was assigned to a new genus (Pegivirus) and renamed as HPgV (Adams et al., 2013;Stapleton et al., 2012a). HPgV has a 9.4 kb positive-sense ssRNA genome that is organized similarly to hepatitis C virus (HCV) (Fig. 1). HPgV and HCV are unusual amongst RNA viruses in that they commonly cause persistent infection in immune-competent humans.Although HPgV is not as efficient at establishing persistent infection as HCV, an estimated 25 % of infections persist and the other 75 % clear viraemia within 2 years of infection (Gutierrez et al., 1997;Tanaka et al., 1998a). The prevalence of HPgV viraemia in cross-sectional serum surveys of healthy blood donors in developed countries is between 1 and 5 %, whilst up to 20 % of blood donors in ...

show abstract

“…Given precedent with other blood-borne pathogens like HIV and hepatitis B virus, efforts to find homologs of HCV have focused on nonhuman primates. To date, these efforts have been unsuccessful (14). Dogs were domesticated as early as 8,000 BCE (16) and, as companion and working animals, occupy a unique niche at the human-animal interface.…”

mentioning

confidence: 99%

“…Since its discovery about 20 y ago (11,12), the origin of hepatitis C virus (HCV) remains obscure largely because a closely related animal virus homolog has not been identified (13,14). Worldwide, 200 million people are chronically infected with HCV (13,15) and are at risk for developing liver fibrosis, cirrhosis, and hepatocellular carcinoma.…”

mentioning

confidence: 99%

Characterization of a canine homolog of hepatitis C virus

Kapoor

Simmonds

Qaisar

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

243

282

View full text Add to dashboard Cite

An estimated 3% of the world's population is chronically infected with hepatitis C virus (HCV). Although HCV was discovered more than 20 y ago, its origin remains obscure largely because no closely related animal virus homolog has been identified; furthermore, efforts to understand HCV pathogenesis have been hampered by the absence of animal models other than chimpanzees for human disease. Here we report the identification in domestic dogs of a nonprimate hepacivirus. Comparative phylogenetic analysis of the canine hepacivirus (CHV) confirmed it to be the most genetically similar animal virus homolog of HCV. Bayesian Markov chains Monte Carlo and associated time to most recent common ancestor analyses suggest a mean recent divergence time of CHV and HCV clades within the past 500-1,000 y, well after the domestication of canines. The discovery of CHV may provide new insights into the origin and evolution of HCV and a tractable model system with which to probe the pathogenesis, prevention, and treatment of diseases caused by hepacivirus infection.flavivirus | zoonosis

show abstract

The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae

Cited by 254 publications

References 125 publications

Characterization of nonprimate hepacivirus and construction of a functional molecular clone

Characterization of nonprimate hepacivirus and construction of a functional molecular clone

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Characterization of a canine homolog of hepatitis C virus

Contact Info

Product

Resources

About