Role of RRV ORF52 in Virion Maturation

Rhesus monkey rhadinovirus (RRV) is a close relative of the human pathogen, Kaposi’s Sarcoma-Associated Herpesvirus (KSHV). Primary infection with KSHV in culture is highly inefficient and it predominantly adopts a latent phenotype, expressing only a minimal number of viral genes and producing no progeny virions. This contrasts with RRV in culture, which replicates to high viral titer and produces abundant progeny virions, making it a useful model to study gammaherpesvirus lytic replication, virion structure, and the potential roles of tegument proteins in the biology of gammaherpesviruses. Initial work in our laboratory determined that the RRV virion was composed of 33 virally encoded proteins. Of these, 17 are tegument proteins, five of which are unique to the gammaherpesvirus subfamily. ORF52 is one of these five gammaherpesvirus specific tegument proteins and is the focus of this dissertation. This protein is highly abundant within the virion (approximately 1000 copies per particle) and it is closely associated with the capsid. Our results describe a critical role for ORF52 in the cytoplasmic-based later stages of virion morphogenesis. Without ORF52, capsids fail to undergo tegumentation, which is necessary for final envelopment and production of fully infectious virions. In a later section of this dissertation, we also describe preliminary data proposing that ORF52 may play a direct or indirect role in virion transport through interaction with cellular microtubules.