Human herpes simplex viruses (HSV-1 and HSV-2) cause significant morbidity and mortality in neonatal and immunocompromised populations. HSVs are cytolytic viruses which have profound impacts on their host cells. The broad, long-term objective of our research program is to understand the regulation of HSV infection in human cells. This research plan focuses on two representative, highly modified HSV proteins. The hypothesis being tested is that viral protein modification acts as a means to regulate HSV replication. The goal of the first specific aim is to use a combination of molecular genetics and cell biology techniques to determine the function of modified, nuclear VP22 during HSV infection. In the second specific aim, the goal is to combine genetic and physical biochemical analyses to correlate ICP22 posttranslational modifications with its function as a regulator of HSV replication. These studies will determine whether viral protein modifications are necessary processes in the replication of HSV. Since the focus is on key features of virus-host interactions, our findings are of importance to studies of other related human viruses. In the long term, this research will help define the molecular basis of regulation of the life cycle of these important human pathogens.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Experimental Virology Study Section (EVR)
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Beisel, Christopher E
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Mount Sinai School of Medicine
Schools of Medicine
New York
United States
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Cotter, Christopher R; Kim, Won-keun; Nguyen, Marie L et al. (2011) The virion host shutoff protein of herpes simplex virus 1 blocks the replication-independent activation of NF-ýýB in dendritic cells in the absence of type I interferon signaling. J Virol 85:12662-72
Bowles, Robert N; Blaho, John A (2011) A truncation mutation of the neurovirulence ICP22 protein produced by a recombinant HSV-1 generated by bacterial artificial chromosome technology targets infected cell nuclei. J Neurovirol 17:559-69
Cotter, Christopher R; Nguyen, Marie L; Yount, Jacob S et al. (2010) The virion host shut-off (vhs) protein blocks a TLR-independent pathway of herpes simplex virus type 1 recognition in human and mouse dendritic cells. PLoS One 5:e8684
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