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e-Research: A Journal of Undergraduate Work

Abstract

Viruses establish infection by overtaking host cell processes and developing mechanisms that promote viral replication. Herpes simplex virus undergoes lytic and latent cycles of infection throughout the lifespan of its host. The viral genome is transcriptionally silent during latency, but viral proteins are produced upon reactivation. Herpes simplex virus type 1 encodes the ICP0 protein, an E3 ubiquitin ligase required for reactivation from latency of the infectious virus. The immediate-early protein ICP0 regulates the herpes simplex virus by activating viral gene expression thereby initiating lytic infection. Cellular proteins are degraded by ICP0, promoting the virus to enter the lytic cycle. Two cellular histone ubiquitin ligases, RNF8 and RNF168 that promote recruitment of DNA repair factors to DNA damage sites. ICP0 viral expression counteracts RNF8 and RNF168 as anti-viral factors by their degradation. This study maps regions of RNF168 required for its degradation so that proteins involved in viral reactivation can be determined. RNF168 has been shown to organize the DNA damage response by increasing the local concentration of ubiquitinated proteins in damage sites to prolong the ubiquitination signal. As a chromatin-associated RING finger protein, RNF168 consists of a sequence of two motif interacting with ubiquitin (MIU) domains that allow RNF168 to be recruited to damage sites. Two constructs were created, which separated each MIU to test for degradation by ICP0, thus localizing how ICP0 targets cellular proteins. In understanding how ICP0 targets its cellular substrates, other proteins targeted by ICP0 with similar motifs may be identified.

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