GB virus C quasispecies detected in plasma and lymphocyte subsets in a natural human infection

Ruiz, Vanesa; Giordano, Mirta; Rivero, Cintia W.; Minassian, María Laura; Cuestas, María Luján; Trinks, Julieta; Mathet, Verónica Lidia; Oubiña, José R.

doi:10.1099/vir.0.019877-0

Cited by 12 publications

(11 citation statements)

References 21 publications

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“…HPgV RNA was present in all 14 study subjects' PBMCs, and in highly purified populations of T-and Blymphocytes (.98 % purity), consistent with previous studies (George et al, 2006;Ruiz et al, 2010 Although HPgV replicates efficiently in humans, with mean serum viral loads typically .1610 7 genome equivalents ml 21 , replication is inefficient in vitro and the production of virus by lymphocytes maintained in culture ex vivo is reduced following T-cell activation (George et al, 2003;Rydze et al, 2012). Consistent with an interaction between HPgV and cell activation, several clinical studies observed a reduction in T-cell activation and proliferation markers in HIV-infected subjects with HPgV co-infection compared with HIV-mono-infected subjects (Bhattarai et al, 2012a;Maidana-Giret et al, 2009;Rydze et al, 2012;Stapleton et al, 2012b).…”

Section: Hpgv Infects Diverse Haematopoietic Cell Types In Vitrosupporting

confidence: 76%

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

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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 ...

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Section: Hpgv Infects Diverse Haematopoietic Cell Types In Vitrosupporting

confidence: 76%

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

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“…To study GBV-C cpz NS5A/B sequence heterogeneity, six clones each from chimpanzees Candie and 1855 were compared with the consensus sequence (the sequence which occurs with the highest frequency for each nucleotide position; Ruiz et al , 2010). Chimpanzee Candie had only one of six clones identical to the consensus sequence after 4 years of infection, resulting in a heterogeneity index of 0.83 (the proportion of GBV-C cpz clones not bearing the predominant sequence) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…GBV-C cpz NS5A/B sequence diversity was detected in chimpanzees with persistent infection and not in a chimpanzee with transient GBV-C cpz infection, suggesting that the generation of sequence diversity may require persistent infection. Human GBV-C quasispecies have nucleotide substitution rates of up to 8.7 % in the 5′ NTR region, 2.0 % in the E2 region and 3.3 % in the NS3 region (Ruiz et al , 2010; Zampino et al , 1999). We found lower rates of GBV-C cpz NS5A/B nucleotide substitution in chimpanzees, with rates of 0.7 % (Candie) and 1.0 % (1855) in the NS5A/B region.…”

Section: Discussionmentioning

confidence: 99%

“…Positive selection was not detected ( d N / d S ratio <1) in the two chimpanzees with persistent infection, suggesting a lack of immunological selective pressure. Even though sequence diversity was detected, a minority of sequences predominated in human GBV-C and GBV-C cpz during persistent infection (Radkowski et al , 1999; Ruiz et al , 2010). The mutation rate observed between early and late samples during persistent infection was only 0.2–1.5 %, and none of the mutations resulted in a change in the amino acid sequence.…”

Section: Discussionmentioning

confidence: 99%

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The natural history of non-human GB virus C in captive chimpanzees

Mohr

Murthy

McLinden

et al. 2010

Journal of General Virology

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GB virus C (GBV-C) is a common, non-pathogenic human virus that infects lymphocytes. Persistent GBV-C infection of humans with coexistent human immunodeficiency virus (HIV) infection is associated with prolonged survival, and GBV-C replication inhibits HIV replication in vitro. A GBV-C virus variant was identified in chimpanzees in 1998 and was named GBV-Ctrog or GBV-Ccpz. The prevalence and natural history of GBV-C in chimpanzees remains uncharacterized. We examined the sera from 235 captive chimpanzees for the presence of GBV-C viraemia, viral persistence and clearance, E2 antibody kinetics and RNA sequence diversity. Sequences from six isolates shared more sequence identity with GBV-Ccpz than with human GBV-C. The prevalence of GBV-Ccpz viraemia and E2 antibody in chimpanzees (2.5 and 11 %, respectively) was similar to human GBV-C prevalence in healthy human blood donors (1.8 and 9 %, respectively). Persistent GBV-Ccpz infection occurred in two of the six viraemic animals and was documented for 19 years in one animal. Host subspecies troglodyte GBV-C isolates and published verus GBV-C isolates shared a high degree of sequence identity, suggesting that GBV-C in chimpanzees should be identified with a chimpanzee designation (GBV-Ccpz). The prevalence and natural history of chimpanzee GBV-C variant (GBV-Ccpz) appears to be similar to human GBV-C infection. The chimpanzee could serve as an animal model to study HIV–GBV-C co-infection.

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“…Within an individual, HPgV exists as a population of related, yet distinct, viral variants implying that viral adaptation occurs within individuals as well. 76,[94][95][96][97] Interestingly, interferon sensitivity and cell tropism may differ among HPgV variants. 77,79,87 Similarly, clinical isolates of HPgV also vary in their ability to replicate in culture, 65,98 suggesting that genotypic diversity may impact virologic phenotype.…”

Section: Subgenomic Analyses Of Hpgv Genotypes and Hpgv Diversity Havementioning

confidence: 99%

Human pegivirus (HPgV) infection in sub‐Saharan Africa—A call for a renewed research agenda

Singh

Blackard

2017

Reviews in Medical Virology

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The human pegivirus (HPgV)-formerly GB virus C-has a beneficial impact on HIV disease progression that has been described in multiple studies. Given the high prevalence of HIV in sub-Saharan Africa and the continuing need to suppress HIV replication, this review provides a comprehensive overview of the existing data on HPgV infection in sub-Saharan Africa, with a particular focus on studies of prevalence and the circulating HPgV genotypes. This review also highlights the need for additional studies of HPgV conducted on the African continent and proposes a research agenda for evaluation of HPgV.

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GB virus C quasispecies detected in plasma and lymphocyte subsets in a natural human infection

Cited by 12 publications

References 21 publications

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

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

The natural history of non-human GB virus C in captive chimpanzees

Human pegivirus (HPgV) infection in sub‐Saharan Africa—A call for a renewed research agenda

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