Mechanism of apoptosis activation in T lymphocytes by herpes simplex virus

Abstract

Herpes simplex virus (HSV), a large DNA containing virus, is endemic in all human population investigated. After infection of mucocutaneuos surfaces, HSV establishes a latent infection in nerve cells. Various immune evasion mechanisms have been shown to be utilized by HSV including apoptosis induction in T lymphocytes. However, the mechanisms of T cell infection and apoptosis by HSV are still unknown. This study investigated the molecular mechanisms of apoptosis induction in T cells by HSV. The Jurkat T cell line was used as a representative for T cells. The numbers of HSV-infected T cells were determined by immunofluorescent assay (IFA) and flow cytometry. The data suggested that flow cytometry was more sensitive than IFA since infected cells were demonstrated since 2 h p.i. whereas 6 h infection was required for IFA. For apoptosis induction by HSV, Annexin V binding assay demonstrated that both HSV-1 and HSV-2 induced apoptosis in Jurkat cells and caspase-3, -8, and -9 inhibitors blocked apoptosis induced by HSV-1 suggesting that HSV-1 and HSV-2 induced apoptosis in T lymphocytes by caspase-dependent pathways. However, apoptosis might occur through other mechanism(s) since caspase inhibitors used in this study could not completely inhibit apoptosis induced by HSV infection. In addition, the data demonstrated that the numbers of apoptotic cells induced by HSV-2 was significantly higher than by HSV-1 at 12 h p.i. (p= 0.003). Further studies in peripheral blood T cells and the proteins of viruses involved in apoptosis induction should be further performed in order to elucidate the molecular mechanism of apoptosis induced by these viruses