Varicella (chicken pox) is caused by infection with varicella-zoster virus (VZV). Primary infection with VZV is associated with severe infection in immunocompromised children. Varicella has been considered a benign illness in otherwise healthy children. However, with effective vaccines for other childhood viral infections varicella has emerged as a significant cause of serious illness in the general population. Research concerning VZV has been difficult because of the cell-associated nature of VZV replication in vitro and the lack of animal models for the investigation of VZV pathogenesis. The purpose of this study is to evaluate the strain 2 guinea pig as a model of acute primary VZV infection and of the immune response to primary VZV infection. The guinea pig is uniquely susceptible to infection with human VZV. A viremic phase following inoculation with VZV has been demonstrated in the strain 2 guinea pig. The occurrence of viremia suggests that the guinea pig model can be exploited as an analogue of primary human varicella since viremia appears to be fundamental to the pathogenesis of the initial infection with VZV in the human host. The investigation of the guinea pig as a model of VZV immunity is important given recent efforts to prepare a VZV vaccine. This study will investigate immunity to VZV in the strain 2 guinea pig after inoculation with infectious VZV for comparison with immunity to the virus that can be elicited by immunization with VZV proteins. VZV proteins antigens will be prepared by immunoaffinity using murine monoclonal antibodies to specific VZV proteins. Humoral immunity will be measured by solid phase radioimmunoassay for VZV IgG and IgM antibodies, by VZV neutralization assay and by immune transfer (Western blot). Cellular immunity will be assessed by in vitro T-lymphocite proliferation of peripheral blood mononuclear cells stimulated with VZV antigen. Methods to optimize the detection of viremia will be investigated to facilitate the use of the model to evaluate approaches for restricting VZV replication in vivo. Viral culture of peripheral blood mononuclear cells will be done in parallel with an immunofluorescence method which uses monoclonal antibody to detect VZV antigens on these cells. In situ hybridization with radiolabeled cloned fragments of VZV DNA will be evaluated for the identification of the virus in peripheral blood cells. Protection against viremia will be used as an in vivo biologic measure of the efficacy of immunization with VZV proteins antigens, passive antibody to VZV and antiviral drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022280-03
Application #
3133225
Study Section
Experimental Virology Study Section (EVR)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Arvin, A M (1996) Immune responses to varicella-zoster virus. Infect Dis Clin North Am 10:529-70
Arvin, A M; Moffat, J F; Redman, R (1996) Varicella-zoster virus: aspects of pathogenesis and host response to natural infection and varicella vaccine. Adv Virus Res 46:263-309
Lowry, P W; Sabella, C; Koropchak, C M et al. (1993) Investigation of the pathogenesis of varicella-zoster virus infection in guinea pigs by using polymerase chain reaction. J Infect Dis 167:78-83
Sabella, C; Lowry, P W; Abbruzzi, G M et al. (1993) Immunization with the immediate-early tegument protein (open reading frame 62) of varicella-zoster virus protects guinea pigs against virus challenge. J Virol 67:7673-6
Lowry, P W; Solem, S; Watson, B N et al. (1992) Immunity in strain 2 guinea-pigs inoculated with vaccinia virus recombinants expressing varicella-zoster virus glycoproteins I, IV, V or the protein product of the immediate early gene 62. J Gen Virol 73 ( Pt 4):811-9
Hayward, A R; Burger, R; Scheper, R et al. (1991) Major histocompatibility complex restriction of T-cell responses to varicella-zoster virus in guinea pigs. J Virol 65:1491-5
Koropchak, C M; Graham, G; Palmer, J et al. (1991) Investigation of varicella-zoster virus infection by polymerase chain reaction in the immunocompetent host with acute varicella. J Infect Dis 163:1016-22
Arvin, A M; Koropchak, C M; Sharp, M et al. (1990) The T-lymphocyte response to varicella-zoster viral proteins. Adv Exp Med Biol 278:71-81
Koropchak, C M; Solem, S M; Diaz, P S et al. (1989) Investigation of varicella-zoster virus infection of lymphocytes by in situ hybridization. J Virol 63:2392-5

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