Erick McCloskey

Upwards of 80% of people in the world are living with herpes simplex virus 1 (HSV-1). Infections with HSV-1 are lifelong and can cause a range of issues, like painful sores, blindness, or deadly encephalitis in infants and neonates. One unique aspect of HSV-1 infection is the ability of the virus to become latent in sensory neurons. Reactivation from this latent stage leads to recurrent HSV-1 diseases. Infected cell protein 0 (ICP0) is one of the first proteins to be expressed by HSV-1. It is an E3 ubiquitin ligase that enhances expression of all three HSV-1 gene classes (immediate-early, early, and late), leading to efficient lytic replication and reactivation from latency. This transactivation function of ICP0 is linked to dimerization via its C-terminal domain, but it is currently unknown exactly how this dimerization affects HSV-1 infection. The goal of my research in the Davido lab is to understand how ICP0 dimerization affects the HSV-1 viral life cycle, and to identify mechanisms by which ICP0 binds with itself to mediate these effects. Our hypothesis is that specific residues in the C-terminus of ICP0 facilitate the dimerization and thus stimulate viral gene expression. This knowledge can potentially lead to the development of a novel class of antiviral molecules that inhibit ICP0 dimerization and limit HSV-1 replication and disease progression.