Tegument Envelope Protein Interactions in CMV Envelopment

Human cytomegalovirus (HCMV) is responsible for significant mortality and morbidity in immunocompromised patients and results in neurodevelopmental abnormalities in infants and children infected in-utero. Currently there is no licensed vaccine and antiviral therapies have dose limiting toxicities. Thus, further understanding of the replication of this virus, including mechanisms of virion envelopment, could identify new strategies for vaccine and antiviral drug development. In this proposal, we will define interactions between an essential virion glycoprotein complex, gM/gN, and membrane associated outer tegument proteins that lead to envelopment of the virus in a specialized cellular compartment, the assembly compartment. Recombinant viruses with specific mutations in envelope and outer tegument proteins that result in shared phenotypes of defective envelopment will be used to define of viral glycoprotein/ tegument protein interactions required for virion assembly. In addition to increasing current understanding of herpesvirus assembly, results from these studies could potentially identify novel targets for development of therapeutics to limit replication of this virus.