Varicella-zoster virus (VZV) is the etiologic agent of varicella (chickenpox) and zoster (shingles). While VZV infections are usually benign, they may be severe and life-threatening in immunocompromised individuals, especially cancer patients, transplant recipients, and AIDS patients. Unfortunately, studies on the pathogenesis of and antiviral therapy for VZV infections are hampered because VZV does not cause disease in experimental animals. However, simian varicella, which is caused by simian varicella virus (SVV), clinically and pathogenically resembles human varicella and has been shown to be an excellent animal model for human VZV infections. The overall goal of this research program is to use the simian varicella model as a means to study the pathogenesis of human VZV infections and to develop and test potential VZV subunit vaccines and other antiviral therapies. While VZV and sVV have been shown to be antigenically and genetically related, very little is known about the molecular properties or SVV. Therefore, the first 4 specific aims of this proposal are to 1) determine the structure of the SVV genome, 2) identify regions of homology between sVV and DNAs, 3) characterize the sVV glycoproteins, and 4) identify cross-reacting VZV and SVV glycoproteins. This information will provide a molecular foundation on which to base further studies on the pathogenesis of simian varicella.
Specific aim #5 will determine the immune response to individual SVV glycoproteins in SVV infected monkeys and will investigate the role of these glycoproteins in inducing immunity to simian varicella. Immunization with VZV has been demonstrated to protect monkeys against subsequent challenge with sVV.
Specific aim #6 will determine the immune response to the VZV glycoproteins that may be important in eliciting this immunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI026070-05
Application #
2063209
Study Section
Experimental Virology Study Section (EVR)
Project Start
1988-09-30
Project End
1995-08-31
Budget Start
1992-09-01
Budget End
1995-08-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Gray, W L; Gusick, N J (1996) Viral isolates derived from simian varicella epizootics are genetically related but are distinct from other primate herpesviruses. Virology 224:161-6
Gray, W L; Gusick, N J; Ek-Kommonen, C et al. (1995) The inverted repeat regions of the simian varicella virus and varicella-zoster virus genomes have a similar genetic organization. Virus Res 39:181-93
Gray, W L; Gusick, N J; Fletcher, T M et al. (1995) Simian varicella virus antibody response in experimental infection of African green monkeys. J Med Primatol 24:246-51
Pumphrey, C Y; Gray, W L (1995) DNA sequence of the simian varicella virus (SVV) gH gene and analysis of the SVV and varicella zoster virus gH transcripts. Virus Res 38:55-70
Fletcher 3rd, T M; Gray, W L (1994) Transcriptional analysis of two simian varicella virus glycoprotein genes which are homologous to varicella-zoster virus gpI (gE) and gpIV (gI). Virology 205:352-9
Pumphrey, C Y; Gray, W L (1994) DNA sequence and transcriptional analysis of the simian varicella virus glycoprotein B gene. J Gen Virol 75 ( Pt 11):3219-27
Fletcher 3rd, T M; Gray, W L (1993) DNA sequence and genetic organization of the unique short (US) region of the simian varicella virus genome. Virology 193:762-73
Gray, W L; Gusick, N; Fletcher, T M et al. (1993) Characterization and mapping of simian varicella virus transcripts. J Gen Virol 74 ( Pt 8):1639-43
Fletcher 3rd, T M; Gray, W L (1992) Simian varicella virus: characterization of virion and infected cell polypeptides and the antigenic cross-reactivity with varicella-zoster virus. J Gen Virol 73 ( Pt 5):1209-15
Gray, W L; Pumphrey, C Y; Ruyechan, W T et al. (1992) The simian varicella virus and varicella zoster virus genomes are similar in size and structure. Virology 186:562-72

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