Defining how SLBP promotes infectivity of HCMV

PROJECT SUMMARY / ABSTRACT Stem-loop binding protein (SLBP) is a cellular protein required for the production of replication- dependent histones (RDH). SLBP binds to a conserved stem loop in the 3’ UTR of RDH mRNAs and facilitates their processing in the nucleus, export, and translation in the cytoplasm. To date, no other cellular role for SLBP has been reported. We recently demonstrated that during HCMV infection, RDH mRNA processing and translation is inhibited indicating that SLBP is not performing its only known function. Interestingly, however, we also found that SLBP is required for efficient HCMV productive replication. In the absence of SLBP, similar numbers of progeny virions are produced, but my data suggest a non-virion component of the viral supernatant diminishes infectivity of virus stocks made in the absence of SLBP. Together, these data suggest that HCMV utilizes SLBP for a new, yet uncharacterized function to promote HCMV infectivity. The overarching goal of this proposal is to identify and characterize this novel, pro-viral function of SLBP during HCMV infection. Because the only known function of SLBP requires its ability to bind RNA, I hypothesize that HCMV co-opts the RNA binding function of SLBP to perform a new, pro-viral role required to modulate expression of a secreted factor that affects HCMV infectivity. To test this hypothesis, I will determine the function of SLBP required to promote HCMV infectivity, characterize differences in the secretome during HCMV infection in the presence or absence of SLBP, and determine at which point in a newly infected cell HCMV virus stocks produced in the absence of SLBP are deficient.