PublisherThe University of Arizona.
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AbstractHuman cytomegalovirus (HCMV) exists indefinitely in infected individuals through a latent infection that is poorly characterized in hematopoetic cells. We have previously demonstrated that the UL133-UL138 locus within the ULb' region encodes proteins that are integral membrane proteins that are co-localized to the Golgi and are involved in the regulation of viral replication. UL135 is of interest in that it is predicted to activate viral replication. Given preliminary results, exogenous expression of UL135 outside of the context of infection results in apoptosis in fibroblasts through caspase pathways. UL135 possesses five SH3 domain binding sites; we hypothesize that UL135 functions through its interaction with SH3 domain-containing proteins. To confirm the importance of the SH3 domain binding sites, I mutated three of the five SH3 domain binding sites both individually and collectively. Preliminary studies show that UL135 exhibits decreased ability to induce apoptosis when the SH3 domain binding sites are mutated, which suggests that UL135 is indeed acting to activate viral replication by suppressing UL138, a protein previously identified as necessary in establishing a latent infection. Future directions include repetition of these preliminary experiments in addition to creating viruses with these mutants in order to analyze their effect on latency during infection.
Degree ProgramHonors College
Molecular and Cellular Biology