HSV-1 induces filopodia formation in activated T lymphocytes

Abstract

Herpes simplex virus type 1 (HSV-1) is a widespread pathogen, which has diverse clinical manifestations from mild localized infection to severe systemic infection. The tissue tropism of HSV-1 is mainly epithelial and mucosal cells. However, it can also multiply in T lymphocytes suggesting a cause of viremia. In this study, CD3+CD4-CD8- Jurkat T lymphocytes were used. Under activation, up-regulation of CD69 molecules on cell surface was observed. Increase yield of HSV-1 production in activated T lymphocytes was demonstrated. In addition, most of HSV-1 virion progenies from infected T lymphocytes were released extracellularly, suggesting the cause of dissemination. The mechanism which supports HSV-1 infection in activated T lymphocytes is unclear. In epithelial cells, HSV-1 induce filopodia formation which constructed by actin polymerization to support their infectivity. Moreover, in those type of cell, filopodia formation are regulated by Cdc42, a member of Rho GTPase protein. In this study, the trend of β-actin mRNA expression was increased after HSV-1 infection in both activated and non-activated cell while the statistically different was found at protein level. β-actin expression was overexpressed after HSV-1 infection in activated T lymphocytes and decreased in cytochalasin D (cyto D), an inhibitor of actin polymerization and depolymerization of actin filaments formed, treated cells. This result indicated that actin plays role during HSV-1 entry in activated T cells. Moreover, Cdc42 was induced by HSV-1 whereas the expression of other Rho GTPase proteins was not changed. During viral entry, filopodia formation was observed in HSV-1-infected activated T lymphocytes suggesting filopodia formation might play role in HSV-1 entry in T-lymphocytes similar to epithelial cells. Observation under electron microscope suggested that HSV-1 entered into activated T lymphocytes via fusion and endocytosis pathway. In addition, HSV-1 titer in cyto D treated activated T lymphocytes was decreased indicating that actin polymerization plays role in HSV-1 infection of activated T lymphocytes. In conclusion, in activated T lymphocytes, filopodia formation, induced by HSV-1 infection was constructed by actin polymerization through Cdc42 which then resulted in increased yield of HSV-1 production.