Caspase-Dependent Cleavage of an Immediate Early Herpes Simplex Virus Protein

Abstract

Herpes Simplex Virus 1 (HSV-1) is a member of the Herpesviridae family. All herpesviruses cause life-long infections that shift between latent and lyticand have many treatments but no cures. HSV-1 has a double-stranded, linear DNA genome, stages icosahedralcapsid, and envelope. HSV-1 can cause infections in humans ranging from encephalitis (brain Inflammation) to cold sores. Previous studies have determined that apoptosis is triggered early during HSV-1 infection. A necessary event in the induction of apoptosis is the activation of a specific set of cellular proteases called caspases. The goal of this study was to determine whether specificviral proteins were cleaved by these caspases. During the course of infection the virus expresses different proteins classified as Immediate Early, Early, and Late proteins. These experiments focused on the Immediate Early proteins, ICPO, ICP4 and ICP27, that regulate expression of the early and late viral genes and are required for virus replication. A late viral protein, VP22, was also analyzed. Human carcinoma Hep-2 cells were used for infection and western blots were used to detect the viral protein. Here, we identify the presence of a low molecular weight form of the ICP27 protein in HSV-1 infected cells. The levels of this small form of ICP27 are undetectable when infections are performed in the presence of pan-caspase inhibitors. Together, these results suggest that ICP27 is cleaved in a caspase-dependent manner during infection. Future studies are aimed to confirm this result and elucidate the biological relevance of ICP27 cleavage.