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

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 stimulati...

Full description

Saved in:
Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2015-11, Vol.485, p.116-127
Main Authors: Chivero, Ernest T, Bhattarai, Nirjal, McLinden, James H, Xiang, Jinhua, Stapleton, Jack T
Format: Article
Language:English
Subjects:
Adult
Amino Acid Sequence
Cell Degranulation - drug effects
Cell Line
Coinfection
Female
Flaviviridae Infections - immunology
Flaviviridae Infections - pathology
Flaviviridae Infections - virology
Flavivirus - pathogenicity
Flavivirus - physiology
GBV-C
Gene Expression Regulation, Viral
HIV - physiology
HIV Infections - immunology
HIV Infections - pathology
HIV Infections - virology
Host-Pathogen Interactions
HPgV
Humans
Immune modulation
Infectious Disease
Interferon-gamma
Interleukin-12 - pharmacology
K562 Cells
Killer Cells, Natural - drug effects
Killer Cells, Natural - immunology
Killer Cells, Natural - virology
Male
Middle Aged
Molecular Sequence Data
NK cells
Tyk2
Viral Envelope Proteins - genetics
Viral Envelope Proteins - immunology
Viral Load
Virus Replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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, IFN γ 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 IFN γ 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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2015.07.008