GB Virus Type C Infection Polarizes T-Cell Cytokine Gene Expression Toward a Th1 Cytokine Profile via NS5A Protein Expression

Rydze, Robert T.; Xiang, Jinhua; McLinden, James H.; Stapleton, Jack T.

doi:10.1093/infdis/jis312

Cited by 15 publications

(15 citation statements)

References 15 publications

(34 reference statements)

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“…Consistent with these clinical findings, Rydze et al recently found that in vitro infection of PBMCs, and the expression of the GBV-C NS5A protein in a CD4 + T cell line resulted in increased IL-2, IL-12b and IFN-γ mRNA expression, decreased IL-4 and IL-13 mRNA expression and decreased secretion of IL-10 [53]. These studies further suggest that GBV-C may promote Th1 differentiation and induce a Th1-specific cytokine milieu that is protective against HIV infection and that the NS5A protein contributes to this effect.…”

Section: Gbv-c Interactions With Hivmentioning

confidence: 65%

GB virus C: the good boy virus?

Bhattarai

Stapleton

2012

Trends in Microbiology

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GB virus C (GBV-C) is a lymphotropic human virus discovered in 1995 that is related to hepatitis C virus (HCV). GBV-C infection has not been convincingly associated with any disease; however, several studies found an association between persistent GBV-C infection and improved survival in HIV-positive individuals. GBV-C infection modestly alters T cell homeostasis in vivo through various mechanisms, including modulation of chemokine and cytokine release and receptor expression, and by diminution of T cell activation, proliferation and apoptosis, all of which may contribute to improved HIV clinical outcomes. In vitro studies confirm these clinical observations and demonstrate an anti-HIV replication effect of GBV-C. This review summarizes existing data on potential mechanisms by which GBV-C interferes with HIV, and the research needed to capitalize on this epidemiological observation.

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Section: Gbv-c Interactions With Hivmentioning

confidence: 65%

GB virus C: the good boy virus?

Bhattarai

Stapleton

2012

Trends in Microbiology

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133

145

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“…First, GBV-C viremia is associated with a polarization towards a Th1 cytokine profile in a Sicilian HIV-infected clinical cohort [18], and this pattern of cytokine modulation is recapitulated in a cell culture model [33]. Secondly, GBV-C reduces activation-induced cell death and reactivation of latent HIV in peripheral blood lymphocytes obtained from HIV-infected people with suppressed HIV VL [27].…”

Section: Discussionmentioning

confidence: 99%

“…RNA was extracted from serum and GBV-C RNA amplified and detected using a one-step real-time RT-PCR as described [27]. GBV-C was quantified using a synthetically transcribed GBV-C RNA with measured A260/280 to generate a standard curve as previously described [33]. All samples with a cycle threshold value of >35 were repeated using an independent RNA preparation.…”

Section: Methodsmentioning

confidence: 99%

GB Virus C Infection Is Associated with Altered Lymphocyte Subset Distribution and Reduced T Cell Activation and Proliferation in HIV-Infected Individuals

et al. 2012

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GBV-C infection is associated with prolonged survival and with reduced T cell activation in HIV-infected subjects not receiving combination antiretroviral therapy (cART). The relationship between GBV-C and T cell activation in HIV-infected subjects was examined. HIV-infected subjects on cART with non-detectable HIV viral load (VL) or cART naïve subjects were studied. GBV-C VL and HIV VL were determined. Cell surface markers of activation (CD38+/HLA-DR+), proliferation (Ki-67+), and HIV entry co-receptor expression (CCR5+ and CXCR4+) on total CD4+ and CD8+ T cells, and on naïve, central memory (CM), effector memory (EM), and effector CD4+ and CD8+ subpopulations were measured by flow cytometry. In subjects with suppressed HIV VL, GBV-C was consistently associated with reduced activation in naïve, CM, EM, and effector CD4+ cells. GBV-C was associated with reduced CD4+ and CD8+ T cell surface expression of activation and proliferation markers, independent of HIV VL classification. GBV-C was also associated with higher proportions of naïve CD4+ and CD8+ T cells, and with lower proportions of EM CD4+ and CD8+ T cells. In conclusion, GBV-C infection was associated with reduced activation of CD4+ and CD8+ T cells in both HIV viremic and HIV RNA suppressed patients. Those with GBV-C infection demonstrated an increased proportion of naive T cells and a reduction in T cell activation and proliferation independent of HIV VL classification, including those with suppressed HIV VL on cART. Since HIV pathogenesis is thought to be accelerated by T cell activation, these results may contribute to prolonged survival among HIV infected individuals co-infected with GBV-C. Furthermore, since cART therapy does not reduce T cell activation to levels seen in HIV-uninfected people, GBV-C infection may be beneficial for HIV-related diseases in those effectively treated with anti-HIV therapy.

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“…If GBV-C infection attenuates EBOV pathogenesis, it is possible that this occurs through modulation of the host immune response. In the context of HIV infection, GBV-C has been associated with a reduced production of proinflammatory cytokines and a reduction in T-cell activation in vivo and in vitro (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). Conversely, robust production of proinflammatory cytokines and lymphocyte activation followed by massive T-cell death are thought to play a major role in EBOV pathogenesis and have been associated with poor clinical outcome in retrospective studies (21)(22)(23)(24)(25)(26)(27).…”

mentioning

confidence: 99%

GB Virus C Coinfections in West African Ebola Patients

Lauck

Bailey

Andersen

et al. 2015

J Virol

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In 49 patients with known Ebola virus disease outcomes during the ongoing outbreak in Sierra Leone, 13 were coinfected with the immunomodulatory pegivirus GB virus C (GBV-C). Fifty-three percent of these GBV-C ؉ patients survived; in contrast, only 22% of GBV-C ؊ patients survived. Both survival and GBV-C status were associated with age, with older patients having lower survival rates and intermediate-age patients (21 to 45 years) having the highest rate of GBV-C infection. Understanding the separate and combined effects of GBV-C and age on Ebola virus survival may lead to new treatment and prevention strategies, perhaps through age-related pathways of immune activation.

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GB Virus Type C Infection Polarizes T-Cell Cytokine Gene Expression Toward a Th1 Cytokine Profile via NS5A Protein Expression

Cited by 15 publications

References 15 publications

GB virus C: the good boy virus?

GB virus C: the good boy virus?

GB Virus C Infection Is Associated with Altered Lymphocyte Subset Distribution and Reduced T Cell Activation and Proliferation in HIV-Infected Individuals

GB Virus C Coinfections in West African Ebola Patients

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