Human herpesvirus-6-induced cytokines and lymphocyte anergy.
|Title:||Human herpesvirus-6-induced cytokines and lymphocyte anergy.|
|Abstract:||Human Herpesvirus-6 (HHV-6) is a lymphotropic $\beta$-herpesvirus. Epidemiological studies have shown it to be a major etiologic agent of roseola infantum. HHV-6 has been linked to several illnesses and is also considered an important cofactor in AIDS. Although HHV-6 infects a variety of cells in vivo and in vitro, complete viral replication occurs most efficiently in T lymphocytes. Following primary infection, HHV-6 persists in a latent state and can be reactivated under conditions of acquired or induced immunosuppression. The nature of HHV-6 immunosuppression remains unresolved. To address this, the cytokine repertoire expressed by T cells following HHV-6 infection and the T cell anergy induced by HHV-6 were studied. Results show that HHV-6 infected T cells secreted increased amounts of IL-1$\beta$, IL-6, IL-10, IFN-$\gamma$ and TNF-$\alpha$ when compared to mock-infected T cells. The enhanced cytokine release was mediated by binding of the virus to cells and did not require viral replication. HHV-6 exposed T cells showed a significant impairment in their proliferative response to mitogen as well as to activation signals delivered through surface molecules or other transmembrane pathways. Some virus transcription was required to suppress lymphocyte proliferation. HHV-6 infected T cells express a soluble suppressive factor(s) which inhibits the lymphoproliferative response of uninfected cells. The suppressive factor requires its native conformation for activity and its suppressive activity is reduced when neutralized with anti-HHV-6 serum. NK cytolysis in PBMCs exposed to the suppressor factor could be enhanced by the addition of IL-15. These results suggest a mechanism whereby the immune system may respond to acute immunosupvressive HHV-6 infection.|
|Collection||Thèses, 1910 - 2010 // Theses, 1910 - 2010|