Regulation of HSV-1 infection by the non-homologous end joining machinery

DNA viruses, such as herpes simplex virus 1 (HSV-1), exploit specific host DNA repair mechanisms to assist their replication. More recently, the DNA repair machinery that senses damaged self-DNA was shown to function in the innate immune sensing of viral DNA during infection.

We aim to understand how a specific DNA repair pathway – non-homologous end joining (NHEJ) – affects HSV-1 infection and how this virus exploits or evades these host responses. Our preliminary data indicate that two NHEJ proteins act to restrict HSV-1 in different ways, via activation of innate immune responses or by directly affecting virus replication. This study will provide the mechanistic basis of these observations and compare these data with the other components of the NHEJ machinery and how they regulate HSV-1 infection.

This work will further our knowledge of cell-intrinsic immunity and DNA repair as well as leading to the rational design of improved vaccines and oncolytic viruses.