UC San Diego

Many viruses seek to manipulate the cellular environment during infection by seizing control over host post translational modifications (PTMs) by using viral E3-ubiquitin ligases, phosphatases, and kinases. Some viruses, including the genus of Alphaviruses, encode for a macrodomain, an enzymatic protein domain capable of reversing the PTM of ADP-ribosylation (ADPr). ADPr is found in a diverse range of host processes ranging from DNA damage and repair to protein quality control. When their macrodomains are disrupted, viruses lose infectious capacity, drawing attention to the importance of this modification. Identifying which host proteins are involved with this interaction could be key to understanding how these viruses are functioning and how they are manipulating the cell. The host factors at play are known as PARPs, which stands for poly-ADP-ribose-polymerases. Here, I have explored a number of these host PARPs and found novel ways in which they interact with alphaviruses to restrict viral replication. A number of PARPs are implicated in the interaction, most specifically those that either bear a macrodomain themselves, the macroPARPs of PARP9,14,and 15, or the Zinc Finger PARPS, PARP7,12, and 13. Further exploration of these PARPs, how they interact with both viral proteins and each other, is critical to fully understanding the role that ADP-ribosylation plays in restricting Alphavirus infection, as well as how alphaviruses are subverting that control.