A novel T cell evasion mechanism in persistent RNA virus infection

Jack T Stapleton; Jinhua Xiang; James H McLinden; Nirjal Bhattarai; Ernest T Chivero; Donna Klinzman; Thomas M Kaufman; Qing Chang

Journal article

A novel T cell evasion mechanism in persistent RNA virus infection

Jack T Stapleton, Jinhua Xiang, James H McLinden, Nirjal Bhattarai, Ernest T Chivero, Donna Klinzman, Thomas M Kaufman and Qing Chang

Transactions of the American Clinical and Climatological Association, Vol.125, pp.14-24; discussion 24-6

2014

PMCID: PMC4112695

PMID: 25125715

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Abstract

Hepatitis C virus (HCV) and GB virus type C (GBV-C) are associated with impaired T cell function despite the fact that HCV replicates in hepatocytes and GBV-C in a small proportion of lymphocytes. Recently, we showed that HCV and GBV-C E2-envelope proteins reduce T cell activation via the T cell receptor (TCR) by competing for phosphorylation with a critical kinase in the TCR signaling cascade (Lck). E2 interfered with TCR signaling in E2 expressing cells and in bystander cells. The bystander effect was mediated by virus particles and extracellular microvesicular particles (exosomes). Multiple kinase substrate sites are predicted to reside on viral structural proteins and based on bioinformatic predictions, many RNA virus pathogens may interfere with TCR signaling via a similar mechanism. Identification of T cell inhibitory effects of virus structural proteins may provide novel approaches to enhance the immunogenicity and memory of viral vaccines.

Hepatitis - epidemiology

History, 21st Century

GB virus C - immunology

Hepacivirus - immunology

Humans

Hepacivirus - pathogenicity

Hepacivirus - metabolism

T-Lymphocytes - virology

GB virus C - metabolism

T-Lymphocytes - metabolism

Hepatitis - virology

Hepatitis - metabolism

Viral Envelope Proteins - metabolism

Receptors, Antigen, T-Cell - immunology

GB virus C - pathogenicity

Receptors, Antigen, T-Cell - metabolism

Signal Transduction

Lymphocyte Activation

History, 20th Century

Host-Pathogen Interactions

Animals

Immune Evasion

Hepatitis - immunology

T-Lymphocytes - immunology

Viral Envelope Proteins - immunology

Hepatitis - history

Details

Title: Subtitle: A novel T cell evasion mechanism in persistent RNA virus infection
Creators: Jack T Stapleton - Iowa City, IA
Jinhua Xiang - Iowa City, IA
James H McLinden - Iowa City, IA
Nirjal Bhattarai - Iowa City, IA
Ernest T Chivero - Iowa City, IA
Donna Klinzman - Iowa City, IA
Thomas M Kaufman - Iowa City, IA
Qing Chang - Iowa City, IA
Resource Type: Journal article
Publication Details: Transactions of the American Clinical and Climatological Association, Vol.125, pp.14-24; discussion 24-6
PMID: 25125715
PMCID: PMC4112695
ISSN: 0065-7778
Grant note: R01 AI058740 / NIAID NIH HHS I01 BX000207 / BLRD VA I01 BX001241 / BLRD VA I01 CX000821 / CSRD VA R01-AI58740 / NIAID NIH HHS
Language: English
Date published: 2014
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984094644402771

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