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Jay  C.  Brown
Degree(s): Ph.D.
Graduate School: Harvard University
Primary Appointment: Professor of Microbiology
Research Interests:
Structure and Assembly of the Herpes Simplex Virus Capsid.

Email Address: jcb2g@virginia.edu
Biomedical Sciences Graduate Program(s)
  • Microbiology, Immunology and Infectious Diseases
    • Research Description

    Like all herpesviruses, HSV-1 consists of an icosahedral capsid surrounded by a membrane envelope. The capsid, which contains the virus DNA, is assembled in the infected cell nucleus. A DNA-free capsid shell is first formed and later packaged with DNA. Capsids are assembled from a major structural protein (UL19), three other structural polypeptides and a scaffolding protein. Capsids must be formed in such a way that they are able to release the encapsidated DNA as a new cycle of infection is initiated. Individual steps in capsid assembly and DNA uncoating are regarded as attractive targets for novel therapeutics because they are required for HSV-1 replication and because virus-encoded proteins are the primary components involved. In their basic features, the steps of capsid assembly and DNA egress in HSV-1 are expected to be the same as those for other herpesviruses.

    We are undertaking a new initiative to examine how DNA is released from the capsid to initiate an infection. DNA release or uncoating is being studied beginning with purified DNA-containing capsids and an in vitro uncoating system recently developed in our laboratory. Experiments are carried out to identify the DNA end that emerges first from the capsid and to clarify the nature of heterogeneity observed in the population of DNA-containing capsids. In vitro studies are being complemented with an analysis of DNA uncoating as it occurs in infected cells. This project focuses on identifying protein contacts between the capsid and the nuclear pore, the organelle through which DNA enters the host cell nucleus.

    We are also continuing earlier studies that make use of a cell-free capsid assembly system to examine the way the portal becomes incorporated into the nascent capsid. We are testing the idea that assemlby involves a filamentous aggregate of the scaffolding protein bound to the portal and major capsid proteins. This is proposed to condense in a stepwise fashion to create the procapsid. Finally, in vitro studies are being performed to identify how components of the DNA packaging machinery are assembled on the capsid surface prior to their functoning in DNA translocation.

    Selected Publications
  • Newcomb, W. W., and Brown, J. C. (2007) Uncoating the herpes simplex virus genome. J. Mol. Biol. 370, 633-642.
  • Trus, B. L., Newcomb, W. W., Cheng, N., Cardone, G., Marekov, L., Homa, F. L., Brown, J. C. and Steven, A. C. (2007) Allosteric signaling and a nuclear exit strategy: Binding of UL25/UL17 heterodimers to DNA-filled HSV-1 capsids. Molecular Cell 26, 479-489.
  • Newcomb, W. W., Homa, F. L., and Brown, J. C. (2006) Herpes simplex virus capsid structure: DNA packaging protein UL25 is located on the external surface of the capsid near the vertices. J. Virol. 80: 6286-6294.
  • Newcomb, W. W., Homa, F. L., and Brown, J. C. (2005) Involvement of the portal at an early step in herpes simplex virus capsid assembly. J. Virol. 79, 10540-10546.
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      Office Address: PO Box 800734, Jordan Hall, 7-63, 
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