Faculty
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A. Oveta Fuller |
Herpes simplex virus entry, receptors and viral pathogenesis
We seek to understand molecular mechanisms of how viruses enter cells and how they mediate events of membrane fusion and spread. We study the prevalent human pathogens, herpes simplex viruses (HSV) 1 and 2 and a closely related herpesvirus of porcine- pseudorabies viruses (PRV). Multiple viral ligand-cell receptor attachments trigger the conformational changes required for virus-cell fusion as a particularly critical event in infection. The research provides insight into virus entry, herpesvirus pathogenesis and tropism, protein structure/function, fusion of biological membranes, and control and prevention of viral infections. Results can be applied to design of anti-virals and use of viruses as vectors for gene delivery.
A major focus of studies is molecular characterization of the structure and functions of recently identified human genes that encode cell receptors used by HSV. By expression cloning, we identified human genes that mediate HSV infection of entry-defective porcine cells. Several of these encode novel human proteins. Their structure, functions, viral ligands and how they work alone, or cooperatively, for infection of highly susceptible human cells are dissected in an entry defective porcine cell model. We also are interested in the natural function of the receptor proteins for human cells.
Most recently, we have begun several collaborative investigations with researchers in engineering or public health to develop microchip technology for detection of genetic changes in human pathogens such influenza virus, or to explore involvement of neurotropic viruses in dementia. These studies involve a broad range of approaches in molecular and cell biology, genetics, membrane biology, biochemistry and virology
Selected Publications:
Perez, A. and A.O. Fuller. (1998) Stable attachment for herpes simplex Virus entry requires gD in the virion and receptors that are missing on entry-defective porcine cells. Virus Research 58:21-34.
Fuller, A. O. and Pilar Perez-Romero. (2002) Mechanisms of human DNA virus infection: entry and early events. Frontiers in Bioscience 7:d390-406.
M. Yang, N. Srivastava, R. Lin, M. Burns, M. Solomon, D. Burke, A.O. Fuller , L. Herlocher, R. Larson, The Development of Microfluidic Devices For Influenza A Detection and Genotyping, (2003) Proceedings of the International Conference on Options for the Control of Influenza V, Okinawa, Japan, International Congress Series 1263, Elsevier, New York, pp. 365-371.
Fuller, A.O. The Biology of AIDS. (2004) Invited paper in HIV and AIDS: A Global Pandemic and the Village Crisis. (Editor, P. Jones-Penn, Corporate Press, Inc. Landover, MD) p. 113-120.
Perez-Romero, P., A. Perez, A. A. Capul, N. McLaren, R. Montgomery and A. O.Fuller. (2005) Herpesvirus entry mediator (HVEM) associates in infected Cells in a complex with viral protein gD and at least gH. J. Virol. 79(7): 4540-4544.
Perez-Romero, P. and A.O. Fuller. (2005) The C-terminal coiled coil predicted in the B5 receptor protein functions in herpes simplex virus infection. J. Virol. 79(12):7419-7430.
Perez, A., Q.-X. Li, P. Perez-Romero, G. Delassus, N. McLaren, S. Sutter, and A. O. Fuller. (2005) A new class of cellular receptor for Herpes simplex virus has heptad repeats common to membrane fusion proteins. J. Virol. 79(12):7431-7437.
M. Burns, R. Pal, M. Yang, R. Lin, B.N. Johnson, N. Srivastava, S.Z. Razzacki, K.J. Chomistek, D. Heldsinger, R. M. Haque, V. Ugaz, P. Thwar, Z. Chen, K. Alfano, M.-B. Yim, M. Krishnan, A.O. Fuller, R. Larson, D.Burke, (2005) An Integrated Microfluidic Device for Influenza and Other Genetic Analyses, Lab on a Chip, 5(10): 1024-1032.
