Identifying Susceptibility Factors for KSHV Infection in Human Tonsil

Kaposi Sarcoma (KS) remains among the most common malignancies worldwide. Despite 25 years of KSHV research, fundamental questions remain about how KSHV moves within the human population. Epidemiological studies of KSHV transmission are limited by two major factors: (1) KSHV shedding is rare in immunocompetent hosts and frequent but sporadic in immunosuppressed individuals. (2) Identification of infected individuals is confounded by the fact that KSHV antibody titers vary significantly over time to the extent that seropositive hosts can appear seronegative on subsequent sampling. The experiments proposed here use ex vivo infection of primary human cells to bypass these barriers while still allowing us to examine host- intrinsic factors that influence susceptibility. The Messaoudi Lab will provide their expertise in next generation RNA sequencing (RNAseq) to identify genes that are differentially expressed in highly susceptible samples compared to refractory samples. This approach will identify non-viral factors that influence susceptibility of tonsil lymphocytes to KSHV infection. Second, the Messaoudi Lab will determine whether commensal organisms and/or co-infections influence susceptibility to KSHV infection. Third, the Messaoudi lab will assist with multiplex analysis of immune mediators produced by co-culture experiments. Finally, the Messaoudi lab will assist in data integration and refinement of models for the particular immunological subsets or inflammatory states that influence susceptibility to KSHV infection.