Clinical isolates of GB virus type C vary in their ability to persist and replicate in peripheral blood mononuclear cell cultures

George, Sarah L.; Xiang, Jinhua; Stapleton, Jack T.

doi:10.1016/s0042-6822(03)00585-3

Cited by 47 publications

(67 citation statements)

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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: 87%

“…As noted above, early studies proposed that the virus was hepatotropic; however, several lines of evidence suggest that the virus is lymphotropic (Fogeda et al, 1999;George et al, 2006;Xiang et al, 2000Xiang et al, , 2001. Specifically, PBMCs from HPgVinfected individuals maintained in culture ex vivo release virus into culture media and virus production can persist for at least 35 days in culture (Fogeda et al, 1999;George et al, 2003;Rydze et al, 2012). Furthermore, serumderived virus from infected individuals is capable of infecting PBMCs in vitro (Chivero et al, 2014;Xiang et al, 2000).…”

Section: Hpgv Infects Diverse Haematopoietic Cell Types In Vitromentioning

confidence: 99%

“…The best-characterized in vitro methods described to date for HPgV replication utilize primary PBMCs (Fogeda et al, 1999;George et al, 2003George et al, , 2006Rydze et al, 2012;Xiang et al, 2000). Unfortunately, production of HPgV by donor lymphocytes demonstrates considerable donor and isolate variability (George et al, 2003), and quantification of HPgV in various peripheral blood cell types detects only 1-10 copies per 100 cells on average. Thus, a very small proportion of PBMCs appear to support replication (Chivero et al, 2014).…”

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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: 87%

Section: Hpgv Infects Diverse Haematopoietic Cell Types In Vitromentioning

confidence: 99%

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confidence: 99%

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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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“…As these studies have been conducted in the USA, Japan, Europe, and South America, the impact of GBV-C genotype should be considered when interpreting results. In addition, all in vitro studies done to date examining GBV-C/HIV interactions have utilized a single GBV-C genotype 2 isolate [George et al, 2003;Muerhoff et al, 2005]. It will be of interest to determine whether the same in vitro effects on HIV infectivity are observed in the presence of other GBV-C genotypes.…”

Section: Biological Relevance Of Gbv-c Genotypesmentioning

confidence: 99%

A previously unrecognized sixth genotype of GB virus C revealed by analysis of 5′‐untranslated region sequences

Muerhoff

Dawson

Desai

2005

Journal of Medical Virology

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GB virus C (GBV‐C) is a positive‐strand RNA virus that infects a large proportion of the world's human population. It has been classified tentatively as a member of the Flaviviridae family and has been shown to exist as a group of five closely related genotypes. Recently, we reported the first full‐length genome sequence of a genotype 5 isolate from South Africa [Muerhoff et al. (2005): J Gen Virol 86: 1729–1735]. As part of the analysis of that sequence, a phylogenetic tree was elucidated from the 5′‐untranslated region (UTR) that showed excellent congruence to the tree produced by analysis of complete open reading frame sequences. When 5′‐UTR analysis was broadened subsequently to include additional isolates from around the globe, a heretofore unrecognized GBV‐C genotype was discovered in Indonesia. When first reported in 2000 [Handajani et al. (2000): J Clin Microbiol 38:662–668], these isolates were described as constituting a novel fifth genotype. However, comparison to isolates from the then‐known fourth and fifth genotypes (from Myanmar/Vietnam and South Africa, respectively) was not performed. A dataset of 121 GBV‐C 5′‐UTR sequences was complied and included representatives of the fourth and fifth genotypes as well as the “novel” Indonesian sequences and demonstrated, with strong support via bootstrap analysis, the existence of a sixth GBV‐C genotype among infected individuals in Indonesia. The discovery of this sixth genotype emphasizes the diverse nature of GBV‐C isolates and may have important implications for the interpretation of studies involving GBV‐C/HIV co‐infected individuals. J. Med. Virol. 78:105–111, 2006. © 2005 Wiley‐Liss, inc.

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“…GBV-C RNA has recently been identified in purified CD4 + and CD8 + T lymphocytes (TL), as well as in CD19 + B lymphocytes (BL) removed ex vivo from infected donors and it has been found that GBV-C replicates in vitro in these peripheral blood mononuclear cell (PBMC) subsets, which suggests that GBV-C is a panlymphotropic virus (Fogeda et al, 1999;George et al, 2003George et al, , 2006.…”

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confidence: 99%

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

Ruiz

Giordano

Rivero

et al. 2010

Journal of General Virology

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Genomic heterogeneity and quasispecies composition of GB virus C (GBV-C) within plasma and lymphocyte subsets in a naturally infected blood donor were investigated. For this purpose, fragments from the 59 untranslated region (59 UTR) and the E2 gene recovered from plasma, B and T lymphocytes, were cloned and sequenced. A total of 63 clones was analysed: 95.2 % of them (n560) -obtained from plasma and cells -were assigned to genotype 2b, while only three derived from plasma corresponded to genotyope 3. The G215A transition within this region was present in 90.9 % of the clones from B lymphocytes, but absent in the remaining cell compartments (P,0.01). Apparently, most of the circulating GBV-C quasispecies in this blood donor were related to the viral population infecting CD8 + T cells, and B cells to a lesser extent. This is the first report showing the quasispecies nature of GBV-C in lymphocyte subsets within peripheral blood mononuclear cells.

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Clinical isolates of GB virus type C vary in their ability to persist and replicate in peripheral blood mononuclear cell cultures

Cited by 47 publications

References 33 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

A previously unrecognized sixth genotype of GB virus C revealed by analysis of 5′‐untranslated region sequences

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

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