THE ROLE OF PHOSPHATIDYLCHOLINE TRANSFER PROTEIN IN HUMAN CYTOMEGALOVIRUS REPLICATION

Abstract

Human cytomegalovirus (HCMV) is a widely-spread -herpesvirus that causes congenital infection resulting in devastating disabilities in newborns. HCMV requires viral remodeling of host cell metabolism to obtain metabolites and lipids to support replication and contains an envelope made of lipids ‘stolen’ from the host. Envelopment is a crucial step in the HCMV life cycle and requires numerous host cell lipids, including phosphatidylcholines (PC). PC lipids are transferred between membranes by phosphatidylcholine transfer protein (PC-TP). I hypothesize that infection requires the transfer of PC lipids from their site of synthesis to the site of HCMV envelopment via PC-TP. I found that HCMV upregulates PC-TP expression during infection, suggesting that it is important to infection. To determine the role of PC-TP in virus replication, I used a small molecule inhibitor and a CRISPR/Cas9 knockout of PC-TP. My preliminary data indicates that the loss of PC-TP activity reduces HCMV infection late in the viral replication cycle, consistent with my hypothesis. Additionally, I analyzed how the loss of PC-TP affects HCMV remodeling of host lipid metabolism. Overall, my preliminary findings demonstrate a possible role for PC-TP in viral replication and provide greater insight into HCMV’s ability to rewire host cells to support infection.