Human Pegivirus (HPgV; formerly known as GBV-C) inhibits IL-12 dependent natural killer cell function

Ernest T Chivero; Nirjal Bhattarai; James H McLinden; Jinhua Xiang; Jack T Stapleton

doi:10.1016/j.virol.2015.07.008

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Human Pegivirus (HPgV; formerly known as GBV-C) inhibits IL-12 dependent natural killer cell function

Journal article

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Peer reviewed

Human Pegivirus (HPgV; formerly known as GBV-C) inhibits IL-12 dependent natural killer cell function

Ernest T Chivero, Nirjal Bhattarai, James H McLinden, Jinhua Xiang and Jack T Stapleton

Virology (New York, N.Y.), Vol.485, pp.116-127

11/2015

DOI: 10.1016/j.virol.2015.07.008

PMCID: PMC5744589

PMID: 26245365

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Abstract

Human Pegivirus (HPgV, formally GB virus C) infects lymphocytes and NK cells in vivo, and infection is associated with reduced T cell and NK cell activation in HIV-infected individuals. The mechanism by which HPgV inhibits NK cell activation has not been assessed. Following IL-12 stimulation, IFNγ expression was lower in HIV-HPgV co-infected subjects compared to HIV mono-infected subjects (p=0.02). In addition, HPgV positive human sera, extracellular vesicles containing E2 protein, recombinant E2 protein and synthetic E2 peptides containing a predicted Tyk2 interacting motif inhibited NK cell IL-12-mediated IFNγ release. E2 protein also inhibited Tyk2 activation following IL-12 stimulation. In contrast, cytolytic NK cell function was not altered by HPgV. Inhibition of NK cell-induced proinflammatory/antiviral cytokines may contribute to both HPgV persistence and reduced immune activation during HIV-coinfection. Understanding mechanisms by which HPgV alters immune activation may contribute towards novel immunomodulatory therapies to treat HIV and inflammatory diseases. •Human Pegivirus (HPgV) was formerly called GB virus C interacts with NK cells.•HPgV particles inhibited NK cell release of IFN-γ following IL-12 stimulation.•A peptide within the HPgV E2 protein was sufficient to inhibit NK cell function.•This peptide inhibited Tyk2 and STAT 4 activation and tyrosine was required.•HPgV did not inhibit the cytolytic functions of NK cells.

NK cells

Tyk2

HPgV

GBV-C

Immune modulation

Details

Title: Subtitle: Human Pegivirus (HPgV; formerly known as GBV-C) inhibits IL-12 dependent natural killer cell function
Creators: Ernest T Chivero - The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA
Nirjal Bhattarai - The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA
James H McLinden - The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA
Jinhua Xiang - The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA
Jack T Stapleton - The Iowa City Veterans Affairs Medical Center The University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Virology (New York, N.Y.), Vol.485, pp.116-127
DOI: 10.1016/j.virol.2015.07.008
PMID: 26245365
PMCID: PMC5744589
NLM abbreviation: Virology
ISSN: 0042-6822
eISSN: 1096-0341
Publisher: Elsevier Inc
Language: English
Date published: 11/2015
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984094347402771

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