Inhibition of TCR signaling by herpes simplex virus. Academic Article uri icon

Overview

abstract

  • T lymphocytes are an essential component of the immune response against HSV infection. We previously reported that T cells became functionally impaired or inactivated after contacting HSV-infected fibroblasts. In our current study, we investigate the mechanisms of inactivation. We report that HSV-infected fibroblasts or HSV alone can inactivate T cells by profoundly inhibiting TCR signal transduction. Inactivation requires HSV penetration into T cells but not de novo transcription or translation. In HSV-inactivated T cells stimulated through the TCR, phosphorylation of Zap70 occurs normally. However, TCR signaling is inhibited at linker for activation of T cells (LAT) and at steps distal to LAT in the TCR signal cascade including inhibition of calcium flux and inhibition of multiple MAPK. Inactivation of T cells by HSV leads to the reduced phosphorylation of LAT at tyrosine residues critical for TCR signal propagation. Treatment of T cells with tyrosine phosphatase inhibitors attenuates inactivation by HSV, and stimulus with a mitogen that bypasses LAT phosphorylation overcomes inactivation. Our findings elucidate a potentially novel method of viral immune evasion that could be exploited to better manage HSV infection, aid in vaccine design, or allow targeted manipulation of T cell function.

publication date

  • February 1, 2006

Research

keywords

  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • Simplexvirus
  • T-Lymphocytes

Identity

Scopus Document Identifier

  • 31144453873

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.176.3.1825

PubMed ID

  • 16424213

Additional Document Info

volume

  • 176

issue

  • 3