Inhibition of TCR signaling by herpes simplex virus

Derek D. Sloan, Jin Young Han, Tracy K. Sandifer, Mary Stewart, Aaron J. Hinz, Miri Yoon, David C. Johnson, Patricia G. Spear, Keith R. Jerome

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1825-1833
Number of pages9
JournalJournal of Immunology
Volume176
Issue number3
DOIs
StatePublished - Feb 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sloan, D. D., Han, J. Y., Sandifer, T. K., Stewart, M., Hinz, A. J., Yoon, M., Johnson, D. C., Spear, P. G., & Jerome, K. R. (2006). Inhibition of TCR signaling by herpes simplex virus. Journal of Immunology, 176(3), 1825-1833. https://doi.org/10.4049/jimmunol.176.3.1825