Fred L. Homa, PhD

Associate Professor


Dr. Homa

Contact

412-648-8788
Fax: 412-624-1401

515 Bridgeside Point II

450 Technology Drive

Pittsburgh, PA 15219

Education

PhD in Biological Chemistry, University of Illinois Medical School

Research Summary

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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Research Lab Affiliation

Publications

Huffman JB, Daniel GR, Falck-Pedersen E, Huet A, Smith GA, Conway JF and Homa FL. 2017. The C-terminus of the herpes simplex virus pUL25 protein is required for release of viral genomes from capsids bound to nuclear pores. J Virol. 91: e00641-17. |  View Abstract

Huet A, Makhov AM, Huffman JB, Vos M, Homa FL and Conway JF. 2016. Extensive subunit contacts underpin herpesvirus capsid stability and interior-to-exterior allostery. Nat Struct Mol Biol. 6: 531-539. |  View Abstract

McNab AR, Desai P, Person D, Roof LL, Thomsen DR, Newcomb WW, Brown JC and Homa FL. 1998. The product of the herpes simplex virus type 1 UL25 gene is required for encapsidation but not for cleavage of replicated viral DNA. J Virol. 72: 1060-1070. |  View Abstract

Thomsen DR, Roof LL and Homa FL. 1994. Assembly of herpes simplex virus (HSV) intermediate capsids in insect cells infected with recombinant baculoviruses expressing HSV capsid proteins. J Virol. 68: 2442-2457. |  View Abstract

Tengelsen L, Pedersen NE, Wathen MW and Homa FL. 1993. Herpes simplex virus type 1 DNA cleavage and encapsidation requires the product of the UL28 gene: isolation and characterization of two UL28 deletion mutants. J Virol. 67: 3470-3480. |  View Abstract