The new R01 will investigate the contribution of a form of gene silencing known as Polycomb silencing in both the establishment of HSV latency and reactivation. Polycomb silencing is a reversible form of gene silencing that regulates the expression of cell-type specific genes during development, and it can also be deregulated in cancer. HSV establishes a latent infection in fully differentiated neurons, where little is known about the mechanisms of Polycomb silencing and its role in gene silencing. A former graduate student and postdoc in the Cliffe lab, Sara Dochnal, PhD, found that Polycomb silencing of HSV DNA plays an important role in allowing HSV to become latent in neurons in a way that can also permit the virus to reactivate. The study aims to understand the mechanisms by which Polycomb silencing permits the formation of a reactivation-competent latent infection. The Cliffe lab will also investigate how a viral non-coding RNA expressed in neurons promotes Polycomb silencing on the HSV-1 genome to enable latency establishment in a way primed for reactivation. The long-term goal is to develop therapeutics that can prevent reactivation by ultimately manipulating the type of gene silencing on the HSV-1 genome. [more]
Congratulations to the Cliffe Lab!