Work

The Us3 Protein of Herpes Simplex Virus 1 Inhibits T Cell Signaling by Confining Linker for Activation of T Cells (LAT) Activation via TRAF6 Protein

Year: 2015

Type: article

Abstract: Herpes simplex virus 1 (HSV-1) is the most prevalent human virus and causes global morbidity because the virus is able to infect multiple cell types. Remarkably, HSV infection switches between lytic and latent cycles, where T cells play a critical role. However, the precise way of virus-host interactions is incompletely understood. Here we report that HSV-1 productively infected Jurkat T-cells and inhibited antigen-induced T cell receptor activation. We discovered that HSV-1-encoded Us3 protein interrupted TCR signaling and interleukin-2 production by inactivation of the linker for activation of T cells. This study unveils a mechanism by which HSV-1 intrudes into early events of TCR-mediated cell signaling and may provide novel insights into HSV infection, during which the virus escapes from host immune surveillance. Background: HSV-1 inhibits T cell functions, but the underlying mechanism is unclear. Results: The HSV-1 Us3 protein disrupts T cell signal transduction by inhibiting the ubiquitination of LAT. Conclusion: The Us3 protein is a crucial factor to suppress T cell activation in HSV-1 infection. Significance: Inhibition of T cell immunity may promote HSV-1 replication or persistence.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m115.646422