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Fred L. Homa, PhD

Dr. Fred Homa


Fax: 412-624-1404
515 Bridgeside Point II
450 Technology Drive


PhD in Biochemistry, University of Illinois Medical School

BA in Biology, North Central College

Academic Affiliation(s)

Associate Professor, Department of Microbiology and Molecular Genetics

Member, Molecular Virology and Microbiology Graduate Program

Member, Molecular Genetics and Developmental Biology Graduate Program


Research in our lab is focused on understanding the mechanism of herpesvirus capsid assembly and DNA packaging.  The structure of the HSV 1 capsid was determined from three-dimensional image reconstruc¬tions com¬puted from cryo¬-electron micrographs of capsids. The capsid shell is composed predominantly of four proteins, a major capsid protein, VP5, and three less abundant proteins, VP19C, VP23 and VP26.  Herpesvirus DNA is incorporated into preassembled capsids through a ring-shaped portal present at a unique vertex.  This process requires the action of seven cleavage/packaging proteins that interact with the capsid either during capsid assembly or during DNA packaging. The terminase proteins (UL15, UL28, UL33) act as part of an ATP-dependent pump that drives DNA into the procapsid and cut the concatemeric DNA at specific sites yielding 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. The cleavage/packaging and capsid completion reactions can be viewed as separate steps in the overall process of generating a stable DNA-containing capsid.  The main goals of this project are to determine the function(s) of the individual cleavage/packaging proteins in this process in order to achieve a detailed understanding of the HSV DNA cleavage and packaging mechanism.

Ongoing studies are focused at defining the role of the UL25 protein in DNA packaging with regards to its functions in retention of viral DNA by binding to capsid vertices through its interaction with the UL17 protein.  Genetic and biochemical approaches are being be used to determine the role of the UL15, UL28, and UL33 proteins in the assembly of a functional terminase complex and their interactions with each other, the portal and viral DNA.  These studies utilize genetic and biochemical approaches to understand how the protein complexes assemble and carry out the cleavage/packaging reaction. In collaboration with Dr. James Conway’s lab (Department of Structural Biology) molecular genetics and cryo-electron microscopy (cryoEM) are being used to obtain high resolution models of the herpesvirus capsid and the essential minor proteins that interact with the capsid during and following DNA packaging. The locations of most of these essential minor proteins are not known nor are details of their interactions with each other and the capsid.  The knowledge obtained from these studies enables not only a significantly better understanding of herpesvirus capsid structure, but also provides the means to reveal aspects of how the viral DNA packaging machinery interacts with the capsid during and after DNA packaging.

Lab Personnel

Jamie Huffman, Research Technician


Toropova K, Huffman J. B, Homa F. L, and Conway J. F. The herpes simplex virus 1 UL17 protein is the second constituent of the capsid vertex-specific component required for DNA packaging and retention. J Virol. 85: 7513-7522. |  View Abstract

Cockrell S. K, Huffman J. B, Toropova K, Conway J. F, and Homa F. L. Residues of the UL25 protein of herpes simplex virus that are required for its stable interaction with capsids. J Virol. 85: 4875-4887. |  View Abstract

Conway J. F, and Homa F. L. Nucleocapsid structure, assembly and DNA packaging of herpes simplex virus. 2011. In Alphaheresviruses. S. K. Weller, Ed. Caister Academic Press, Norwich, U.K. Pgs. 175-193.

Conway J. F, Cockrell S. K, Copeland A. M, Newcomb W. W, Brown J. C, and Homa F. L. Labeling and localization of the herpes simplex virus capsid protein UL25 and its interaction with the two triplexes closest to the penton. J Mol Biol. 397: 575-586. |  View Abstract

Newcomb W. W, Cockrell S. K, Homa F. L, and Brown J. C. Polarized DNA ejection from the herpesvirus capsid. J Mol Biol. 392: 885-894. |  View Abstract

Cockrell S. K, Sanchez M. E, Erazo A, and Homa F. L. Role of the UL25 protein in herpes simplex virus DNA encapsidation. J Virol. 83: 47-57. |  View Abstract

Huffman J. B, Newcomb W. W, Brown J. C, and Homa F. L. Amino acids 143 to 150 of the herpes simplex virus type 1 scaffold protein are required for the formation of portal-containing capsids. J Virol. 82: 6778-6781. |  View Abstract