Email: Office Phone: 318-675-4706
Laboratory Phone: 318-675-5759
Office Fax: 318-675-5764
Postdoctoral Study, Dartmouth University School of Medicine and Louisiana State University Health Sciences Center - Shreveport
Ph.D. Immunology, 1993, Louisiana State University Health Sciences Center - Shreveport
B.S. Microbiology, 1987, Louisiana State University
Major Research Interests:
Molecular pathogenesis of equine herpesvirus type 1
In its natural host, equine herpesvirus type 1 (EHV-1) can establish a latent infection and/or cause severe respiratory disease that may be accompanied by sequelae involving the central nervous system. EHV-1 respiratory infection in the mouse results in either the generation of a protective immune response or a fatal immunopathological response, depending on the expression of only a very few viral gene products. Using recombinants generated from two parental EHV-1 strains, the attenuated KyA strain and the highly pathogenic RacL11 strain, we have begun to identify those viral gene products capable of eliciting the severe inflammatory response observed in the murine lung and facilitating virus entry and spread into the central nervous system. Specifically, my research has focused on viral glycoproteins encoded within the unique short (Us) segment of the viral genome. Utilizing the technologies of gene cloning, PCR, RNase protection analysis, and DNA array, we have begun to assess how the expression, or lack of expression, of two specific virally-encoded glycoproteins, I (gI) and E (gE), influences the production of proinflammatory chemokines/cytokines within the murine respiratory tract early in infection. In addition, we are investigating the ability of glycoprotein gp2, also encoded within the Us segment and unique to EHV, to elicit severe inflammation in the lung. These studies may begin to delineate molecular mechanisms by which a virus can elicit a fatal immunopathological response in the respiratory tract, gain entry into the central nervous system, and ultimately shift the host immune response from being one of protection to infection to being one of profound immunopathology.
Smith, P. M ., Y. Zhang, S. R. Jennings, and D. J. O'Callaghan. 1998. Characterization of the cytolytic lymphocyte (CTL) responses to a candidate vaccine strain of EHV-1 in CBA mice. J. Virol. 72:5366-5372.
Zhang, Y., P. M. Smith, E. B. Tarbet, N. Osterrieder, S. R. Jennings, and D. J. O'Callaghan. 1998. Protective immunity against equine herpesvirus 1 (EHV-1) infection in mice induced by recombinant EHV-1 gD. Virus Research 56:11-24.
Smith, P. M., Y. Zhang, S. R. Jennings, W. D. Grafton, and D. J. O'Callaghan. 2000. Severe immunopathology in the murine lung elicited by the pathogenic EHV-1 strain RacL11 correlates with the early production of MIP-1a, MIP-1b, MIP-2, and TNFa. J. Virol. 74:10034-10040.
Frampton, A. R., P. M. Smith, Y. Zhang, T. Matsumura, N. Osterrieder, and D. J. O'Callaghan. 2002. Contribution of gene products encoded within the unique short segment of Equine Herpesvirus 1 to virulence in a murine model. Virus Res. 90:287-301.
Frampton, A. R. Jr., P.M. Smith, Y. Zhang, W. D. Grafton, T. Matsumura, and D. J. O'Callaghan. 2004. Meningoencephalitis in Mice Infected with an Equine Herpesvirus 1 Strain KyA Recombinant Expressing Glycoprotein I and Glycoprotein E. Virus Genes. 29:9-17.
Smith, P.M., Kahan, S. M., Rorex, C.B., von Einem, J., Osterrieder, N., and D. J. O’Callaghan. 2005. Expression of the full-length form of gp2 of equine herpesvirus 1 (EHV-1) completely restores respiratory virulence to the attenuated EHV-1 strain KyA in CBA mice. J. Virol. 79(8) 5105-5115.