Kaposi’s Sarcoma-Associated Herpesvirus targeting of CD1c by the K8.1 glycoprotein 4107

Description Kaposi’s Sarcoma is a form of cancer that is primarily caused by infection from Kaposi’s Sarcoma-Associated Herpesvirus (KSHV), the 8th known Human Herpesvirus (HHV8). It is currently understood that CD1 proteins found on specific antigen presenting cells, are a key part of initiating innate & adaptive immune responses. Within the CD1 protein set is a specific protein known as CD1c, which is responsible for activating CD1c-restricted T Cells. Our group found that a KSHV-encoded glycoprotein, K8.1, is able to inhibit expression of CD1c, which may allow KSHV to spread infection more efficiently by avoiding detection. K8.1A, which is the full length K8.1 open reading frame, downregulates CD1c, while K8.1B, which was missing a 61 amino acid domain of the N-terminal side, does not. We hypothesize that this domain in K8.1A is responsible for the downregulation of CD1c by K8.1. We synthesized different K8.1 proteins to determine the protein domains that allow for downregulation of CD1c. We transfected K8.1 protein into HEK293T cells and found that the mutants that we generated all produce proteins at different sizes using western blot and these sizes correspond to different processed forms. Next, we will see how these proteins impact co-transfected CD1c. In conclusion, this work is important towards understanding the mechanism KSHV used to avoid immune activation by downregulating CD1c, and how these methods allow the rapid growth of KSHV in the development of Kaposi’s Sarcoma. Funding Sources This project was funded and supported, in part, by the SPIRES program (NSF grant 1834186) and the CSU-LSAMP program (NSF grant HRD-1826490) at Cal Poly Pomona, as well as NIH Grants 1R03AI172631-01A1 and 1R21CA261297-01 and funds from the Western University of Health Sciences College of Pharmacy. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)