Ann Arvin

Ann Arvin, Professor Pediatrics; Microbiology & Immunology Stanford University Medical Center, G-312, Stanford, CA 94305 Tel: (650) 723-5682 FAX: (650) 725-8040

Our laboratory investigates pathogenesis and the host response to varicella zoster virus (VZV) with projects in three areas, including identification of viral proteins that are major targets of immunity, investigation of cell types associated with permissive and latent viral infection in vivo in humans and in the SCID-hu mouse, and generation of recombinant strains of VZV from cosmids to identify genetic determinants of pathogenicity. Current studies of VZV protein specific immunity include the use of vaccinia recombinants expressing VZV glycoproteins or immediate early/tegument proteins to analyze cytotoxic T-cell responses to VZV and the use of human dendritic cells to sensitize naive T lymphocytes in vitro with VZV peptides. The role of class I and class II restricted CTL responses to VZV is being assessed during primary VZV infection and in persistent immunity to VZV. Vaccinia recombinants expressing truncated forms of VZV gene products are being used to define the protein specificity of the CTL response. Aspects of VZV infection are being investigated in the SCID-hu mouse using in situ hybridization, PCR and other methods. The tropism of VZV for human CD4+ and CD8+ T-cells has been demonstrated in SCID-hu mice, providing a new system for analyzing this critical host-virus interaction. Mutant VZV strains are being developed using VZV cosmids; recombinant strains are being tested for the effects of gene deletions on infectivity for T-cells and skin and on latency. Recombinant strains of herpes simplex virus (HSV) that express VZV proteins are being generated in order to characterize the biologic differences between "homologous" proteins of these two closely related human alpha herpes viruses. The ultimate goal of these studies is to provide information relevant to developing new vaccines for VZV and potentially a combined VZV-HSV vaccine.

Lowry, P.W., Solem, S., Koropchak, C.M., Kinchington, P.E., Ruyechan, W., Hay, J., Arvin, A.M. (1992) Immunity in strain 2 guinea pigs inoculated with vaccinia recombinants expressing varicella-zoster virus glycoproteins I, IV, V or the immediate early gene 62. J Gen Virol 73:811-19.
Arvin, A.M., Sharp, M, M., Sanchez, A., Judd, A.K., Arvin, A.M. (1991). Equivalent recognition of a varicella-zoster virus immediate early protein (IE62) and glycoprotein I by cytotoxic T-lymphocytes of either CD4+ or CD8+ phenotype. J Immunol 146:257-264.
Sabella, C., Lowry, P.W., Abbruzzi, G.M., Koropchak, C.M., Kinchington, P.R., Sadegh-Zadeh, M., Hay, J., Ruyechan, W.T., Arvin, A.M. (1993). Immunization with the immediate-early tegument protein (Open Reading Frame 62) of varicella-zoster virus protects guinea pigs against virus challenge. J. Virol. 67:7673-76.
Moffat, J.F., Stein, M.D., Kaneshima, H., Arvin, A.M. Tropism of Varicella-Zoster Virus for human CD4+ and CD8+ T-lymphocytes and Epidermal Cells in SCID-hu Mice. J. Virol. 69:5236-42.
Lowry, P.W., Koropchak, C.M., Choi, C.H., Mocarski, E.S., Kern, E.R., Kinchington, P.R., Arvin, A.M. The Synthesis and Immunogenicity of Varicella-Zoster Virus Glycoprotein I and Immediate-Early (IE62) Expressed in Recombinant Herpes Simplex Virus-1. In Press.
Mallory, S., Sommer, M., Forghani, B., Kinchington, P., Arvin, A.M. Mutational analysis of varicella-zoster virus (VZV) glycoproteins, gI and gE, in recombinant VZV strains. Submitted.

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