Jay C. Brown

Professor Emeritus, Microbiology, Immunology, and Cancer Biology

Primary Location

PO Box 800734

Primary Phone Number

434.924.1814

[email protected]

Website

https://mic.med.virginia.edu/Brown/

Bio & Overview

Project Title: Pathogenesis of Infections by Herpes Simplex Virus Herpes simplex virus is widespread in the human population with most people exposed during childhood. Nearly all adults have specific antibodies. HSV-1 is best-known as the etiological agent of cold sores and genital lesions, but it also causes a stromal ketatitis, disseminated disease in the newborn and encephalitis in adults. HSV-1 is the leading cause of non-epidemic encephalitis in the U.S. In our laboratory we study the structure and assembly of the HSV-1 virion with the idea that such studies will suggest the nature of novel anti-herpes therapeutic agents directed against the assembly process. Although most of our studies are carried out with HSV-1, it is expected that the results will clarify virus assembly as it occurs in other herpes viruses and perhaps in other virus families as well. All herpesviruses have a tegument, a layer of protein located between the virus membrane and the capsid. The tegument is composed predominantly of virus-encoded proteins that together can account for up to half or more of the total virion protein. Tegument proteins are thought to be those involved in the early stages of infection before progeny virus proteins are synthesized. The goal of our work is to examine the structure and assembly of the herpesvirus tegument. It is expected that the tegument will offer novel targets for anti-viral therapy and the research is designed to uncover such targets. Studies are being carried out with HSV-1, the virus in which the tegument has been most thoroughly characterized. Biochemical analysis, for instance, has shown that the HSV-1 tegument is composed of approximately twenty distinct, virus-encoded protein species whose amounts vary considerably. Many of the tegument proteins are required for HSV-1 replication, and functions have been defined for most. Proposed studies are designed to test the hypothesis that tegument structure is organized around UL36, a large protein bound at the capsid vertices. It is proposed that other tegument proteins are attached to the capsid by way of UL36. Additional questions to be addressed include: Which tegument proteins are located furthest from the capsid? Is there temporal and/or spatial specificity to the way tegument components become attached to the capsid? How does the tegument become detached from the capsid as a new infection is initiated? Can intact teguments be isolated away from capsids?

Academic Information

Department: Microbiology, Immunology, and Cancer Biology

Academic Title: Professor

Primary Education

BA, Biology, Johns Hopkins University, Baltimore, MD, 1964
PhD, Biochemistry, Harvard University, Cambridge, MA, 1969
Postdoc, Molecular Biology, MRC Lab of Molecular Biology, Cambridge UK, 1971

Other Appointments

Professor, MII

Other Affiliations

Professor, Arts & Sciences
Member, Chemical and Structural Biology Program
BIMS
Professor, BIMS

Research Interests

Structure and Assembly of the Herpes Simplex Virus Capsid.

Research Disciplines

Bioinformatics and Genomics
Cancer Biology
Computational Biology
Microbiology
Molecular Biology
Structural Biology

Research Opportunities

Bioinformatics & Genomics
Cancer Biology
Computational Biology
Microbiology
Molecular Biology

Selected Publications

2017

Brown, J. C. (2017). Herpes Simplex Virus Latency: The DNA Repair-Centered Pathway. ADVANCES IN VIROLOGY, 2017. doi:10.1155/2017/7028194

2014

Brown, J. C. (2014). The role of DNA repair in herpesvirus pathogenesis. GENOMICS, 104(4), 287-294. doi:10.1016/j.ygeno.2014.08.005

2013

Kofman, A. V., Letson, C., Dupart, E., Bao, Y., Newcomb, W. W., Schiff, D., . . . Abounader, R. (2013). The p53-microRNA-34a axis regulates cellular entry receptors for tumor-associated human herpes viruses. MEDICAL HYPOTHESES, 81(1), 62-67. doi:10.1016/j.mehy.2013.04.012

2012

Newcomb, W. W., & Brown, J. C. (2012). Internal Catalase Protects Herpes Simplex Virus from Inactivation by Hydrogen Peroxide. JOURNAL OF VIROLOGY, 86(21), 11931-11934. doi:10.1128/JVI.01349-12

Newcomb, W. W., Jones, L. M., Dee, A., Chaudhry, F., & Brown, J. C. (2012). Role of a reducing environment in disassembly of the herpesvirus tegument. VIROLOGY, 431(1-2), 71-79. doi:10.1016/j.virol.2012.05.017

Mingo, R. M., Han, J., Newcomb, W. W., & Brown, J. C. (2012). Replication of Herpes Simplex Virus: Egress of Progeny Virus at Specialized Cell Membrane Sites. JOURNAL OF VIROLOGY, 86(13), 7084-7097. doi:10.1128/JVI.00463-12

Cardone, G., Newcomb, W. W., Cheng, N., Wingfield, P. T., Trus, B. L., Brown, J. C., & Steven, A. C. (2012). The UL36 Tegument Protein of Herpes Simplex Virus 1 Has a Composite Binding Site at the Capsid Vertices. JOURNAL OF VIROLOGY, 86(8), 4058-4064. doi:10.1128/JVI.00012-12

Thompson, J. A., & Brown, J. C. (2012). Role of Coatomer Protein I in Virus Replication.. Journal of virology & antiviral research, 1(2). doi:10.4172/2324-8955.1000102

2011

Brown, J. C., & Newcomb, W. W. (2011). Herpesvirus capsid assembly: insights from structural analysis. CURRENT OPINION IN VIROLOGY, 1(2), 142-149. doi:10.1016/j.coviro.2011.06.003

Kofman, A., Marcinkiewicz, L., Dupart, E., Lyshchev, A., Martynov, B., Ryndin, A., . . . Abounader, R. (2011). The roles of viruses in brain tumor initiation and oncomodulation. JOURNAL OF NEURO-ONCOLOGY, 105(3), 451-466. doi:10.1007/s11060-011-0658-6

2010

Newcomb, W. W., & Brown, J. C. (2010). Structure and Capsid Association of the Herpesvirus Large Tegument Protein UL36. JOURNAL OF VIROLOGY, 84(18), 9408-9414. doi:10.1128/JVI.00361-10

Zhi, G., Chen, X., Newcomb, W., Brown, J., Semmes, O. J., & Kupfer, G. M. (2010). Purification of FANCD2 sub-complexes. BRITISH JOURNAL OF HAEMATOLOGY, 150(1), 88-92. doi:10.1111/j.1365-2141.2010.08217.x

Brown, J. C., Newcomb, W. W., & Wertz, G. W. (2010). Helical Virus Structure: The Case of the Rhabdovirus Bullet. VIRUSES-BASEL, 2(4), 995-1001. doi:10.3390/v2040995

Conway, J. F., Cockrell, S. K., Copeland, A. M., Newcomb, W. W., Brown, J. C., & Homa, F. L. (2010). Labeling and Localization of the Herpes Simplex Virus Capsid Protein UL25 and Its Interaction with the Two Triplexes Closest to the Penton. JOURNAL OF MOLECULAR BIOLOGY, 397(2), 575-586. doi:10.1016/j.jmb.2010.01.043