Viral cyclin control of infection and associated disease (VIR1P.1135)

Abstract

Abstract Gammaherpesviruses (gHV), including Epstein-Barr virus and Kaposi’s sarcoma associated herpesvirus, are lymphotropic viruses, distinctive in their ability to exploit the lymphocytes as their lifelong reservoir. gHV infection is ubiquitous, and can result multiple pathologies in immune-compromised individuals. Murine gHV68 is homologous to the human viruses, and serves as a small animal model. Previously, our lab demonstrated that a conserved virally encoded homolog of host cyclins, (v-cyclin), is critical for specific aspects of gHV68 infection. A virus lacking the v-cyclin is is dramatically defective in reactivation from latency, viral persistence, and progression of disease. Using an enzymatically marked virus, we now identify infected cells during latent infection with v-cyclin sufficient or deficient viruses. We found that cells infected with or without the v-cyclin are not significantly different in infected B cell subset distribution. However, we found the number of cells with detectable levels of gene expression was significantly depressed in the absence of the v-cyclin. These data suggest that the v-cyclin supports active gene expression during latency, likely corresponding to increased reactivation capacity. This system parallels the complex gene expression programs of Epstein Barr virus, and may permit us to distinguish the specific features of infected cells poised for reactivation and virus propagation, along with their relative roles in virus induced pathology.