Fred L. Homa, PhD

The goal of our research is to understand an important step of virus assembly – how the herpes simplex virus type 1 (HSV-1) capsid is assembled and the viral genome is packaged into the viral capsid  and the delivery (uncoating) of the viral genome to the nucleus of newly infected cells. DNA encapsidation and cleavage involves the coordinated interaction of several HSV proteins that are essential for production of infectious virions. How these multi-protein assemblies associate and interact to accomplish this complex task touches on fundamental questions in biology. The HSV-1 genome is translocated into the icosahedral procapsid through a donut-shaped “portal” that is present at one of the 12 vertices of the procapsid. This process is directed by the terminase complex, which consists of the HSV UL15, UL28, and UL33 proteins that function both as part of the ATP-hydrolyzing pump which drives DNA into the capsid, and also as a nuclease that cuts the concatemeric DNA at specific sites to yield a capsid containing the intact genome. The capsid is then stabilized by the addition of the capsid vertex specific component (CVSC), composed of the UL17 and UL25 proteins, which functions to retain the packaged DNA and to signal for nuclear egress of the mature DNA-filled capsid, as well as for nuclear attachment of the incoming, infecting capsid. Seven viral gene products are required for the stable packaging of viral DNA into the preformed HSV procapsid. Orthologs of these HSV DNA packaging genes are found in all three classes (alpha, beta, and gamma) of herpesviruses. Information obtained about the function of these proteins from these studies should therefore apply to other herpesviruses such as human cytomegalovirus, varicella zoster virus and Epstein Barr virus.

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