Inhibition of TCR Signaling by Herpes Simplex Virusстатья из журнала
Аннотация: 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.
Год издания: 2006
Авторы: Derek D. Sloan, Jin-Young Han, Tracy K. Sandifer, M. Kathryn Stewart, Aaron Hinz, Miri Yoon, David C. Johnson, Patricia G. Spear, Keith R. Jerome
Издательство: American Association of Immunologists
Источник: The Journal of Immunology
Ключевые слова: Herpesvirus Infections and Treatments, Cytomegalovirus and herpesvirus research, Poxvirus research and outbreaks
Другие ссылки: The Journal of Immunology (PDF)
The Journal of Immunology (HTML)
PubMed (HTML)
The Journal of Immunology (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 176
Выпуск: 3
Страницы: 1825–1833