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 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.

• Authors: Ernest T Chivero, Nirjal Bhattarai, James H McLinden, Jinhua Xiang, Jack T Stapleton
• Journal: Virology (Virology) Vol. 485 Pg. 116-27 (Nov 2015) ISSN: 1096-0341 [Electronic] United States
• PMID: 26245365 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Published by Elsevier Inc.

Chemical References

• Viral Envelope Proteins
• Interleukin-12
• Interferon-gamma

Topics

• Adult
• Amino Acid Sequence
• Cell Degranulation (drug effects)
• Cell Line
• Coinfection
• Female
• Flaviviridae Infections (immunology, pathology, virology)
• Flavivirus (pathogenicity, physiology)
• Gene Expression Regulation, Viral
• HIV (physiology)
• HIV Infections (immunology, pathology, virology)
• Host-Pathogen Interactions
• Humans
• Interferon-gamma
• Interleukin-12 (pharmacology)
• K562 Cells
• Killer Cells, Natural (drug effects, immunology, virology)
• Male
• Middle Aged
• Molecular Sequence Data
• Viral Envelope Proteins (genetics, immunology)
• Viral Load
• Virus Replication