Protein-Protein Interaction Analysis of Kaposi's Sarcoma-Associated Herpesvirus and its Role in Host Viral Replication

By: Ernst Heinz V. Pulido

Department: Cellular & Molecular Biology

Faculty Advisors: Dr. Erica L. Sanchez, Dr. Robyn Kaake (UCSF), and Dr. Scott Roy

Kaposi’s sarcoma (KS) is epidemic within the AIDS/HIV community, endemic in Africa & other parts of the world, and possess problem to transplant-related surgery. It can cause several serious problems when it affects the lungs, liver, or digestive tract. Kaposi’s Sarcoma Associated Herpesvirus (KSHV) is the etiological agent of KS. Previous studies have demonstrated that KSHV infection changes cellular metabolism that affects viral replication, such as increased glucose metabolism. However, the viral mechanism of how KSHV modifies metabolism is unknown. In addition, previous protein-protein interaction studies found that LANA, KSHV latent protein, binds to PIP4K2a/b/c. PIP4K2a/b/c is found to modulate PI3K-AKT pathway. PI3K-AKT is already known to be modulate by KSHV in the lytic stage and mechanisms are elucidated. However, latent stage proteins, such as LANA, has yet to be explored. Interestingly, the LANA-PIP4K interactions has not studied in detail. I hypothesize that LANA, binding to PIP4K2a/b/c, could modulate viral replication. In this study, cross-linking mass spectrometry and using relevant cell lines will be used to expand the protein-protein interaction network during latency will help verify currently known interaction and find other potential targets. In addition, verifying the LANA-PIP4K interaction and LANA’s role in increase of glucose metabolism enzyme/transporters could help determine if LANA help rewire PI3K-AKT pathway. Once verified, it could be determined if LANA is sufficient or necessary for viral replication. Finally, structural and post translational modification study could help determine potential target to host protein. This study could help understand LANA’s role in glucose metabolism and identify possible therapy to inhibit the interaction between LANA and PIP4K family.