Grant: Operating Grant

All herpesviruses cause lifelong infections and once an individual is infected there is no cure. Herpes simplex virus type 2 (HSV-2) is an important human pathogen that is the main cause of genital herpes, is responsible for devastating neonatal infections, and is fuelling the epidemic transmission of HIV. The incidence of HSV-2 infection is very high and genital herpes is one of the most common sexually transmitted diseases on the globe. For example, roughly 21% of women in Canada and in excess of 50% of women in Sub-Saharan Africa are infected with HSV-2. The impact of HSV-2 infection on the HIV epidemic is staggering. In some regions of Sub-Saharan Africa, it has been estimated that ~25% of new HIV infections can be directly attributed to HSV-2 co-infection. The discouraging failure of a HSV-2 vaccine trial in 2010 highlights the need for greater understanding of the interactions between HSV-2 and its host and the development of new anti-viral strategies. During early stages of virus infection the cell interior presents a hostile environment for the virus. Physical barriers associated with transporting the virus genetic material from the cell periphery to the cell interior, coupled with intrinsic cellular antiviral defenses designed to prevent virus infection, are formidable obstacles to the virus. In order to establish a productive infection HSV-2 must overcome these barriers to infection. Our experiments seek to understand how HSV-2 counteracts these obstacles immediately after infection. Our preliminary data suggest that components present in the infecting virus particle counteract cellular antiviral defense mechanisms and promote the expression of virus genes, which is required for the production of new virus. Understanding how HSV-2 overcomes cellular barriers to infection will reveal new targets for antiviral interventions that can be exploited for the treatment and prevention of new HSV-2 infections and ease the suffering of those already infected.