Abstract

This proposal will characterize antibody recognition sites on envelope glycoproteins of human cytomegalovirus (HCMV). Linear and non-linear antibody binding determinants will be mapped using a panel of antisera and murine monoclonal antibodies generated against a collection of overlapping restriction endonuclease fragments of the glycoprotein genes expressed in prokaryotic vectors and a series of truncated glycoproteins expressed in recombinant eukaryotic systems. Strain specific and strain common antibody recognition sites expressed on glycoproteins from clinical HCMV isolates will be studied with the aid of these antigenic maps and antisera (monoclonal antibodies) and a series of recombinant-derived, truncated glycoproteins from these clinical HCMV isolates. In addition, the proposed studies will examine the relation between HCMV strain variability, strain specific immunity and reinfection in human populations. Because antiviral antibodies play an important role in limiting the severity of HCMV-induced disease in many different patient populations, these studies are relevant to our understanding of the pathogenesis of HCMV infections and are essential to the rational design of effective therapies for treatment and/or prevention of HCMV-induced disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI030105-03
Application #
3145210
Study Section
Virology Study Section (VR)
Project Start
1991-05-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Sanchez, V; Angeletti, P C; Engler, J A et al. (1998) Localization of human cytomegalovirus structural proteins to the nuclear matrix of infected human fibroblasts. J Virol 72:3321-9
Fish, K N; Britt, W; Nelson, J A (1996) A novel mechanism for persistence of human cytomegalovirus in macrophages. J Virol 70:1855-62
Britt, W J (1996) Vaccines against human cytomegalovirus: time to test. Trends Microbiol 4:34-8
Li, L; Coelingh, K L; Britt, W J (1995) Human cytomegalovirus neutralizing antibody-resistant phenotype is associated with reduced expression of glycoprotein H. J Virol 69:6047-53
Fish, K N; Depto, A S; Moses, A V et al. (1995) Growth kinetics of human cytomegalovirus are altered in monocyte-derived macrophages. J Virol 69:3737-43
Boppana, S B; Polis, M A; Kramer, A A et al. (1995) Virus-specific antibody responses to human cytomegalovirus (HCMV) in human immunodeficiency virus type 1-infected persons with HCMV retinitis. J Infect Dis 171:182-5
Harrison, C J; Britt, W J; Chapman, N M et al. (1995) Reduced congenital cytomegalovirus (CMV) infection after maternal immunization with a guinea pig CMV glycoprotein before gestational primary CMV infection in the guinea pig model. J Infect Dis 172:1212-20
Billstrom, M A; Britt, W J (1995) Postoligomerization folding of human cytomegalovirus glycoprotein B: identification of folding intermediates and importance of disulfide bonding. J Virol 69:7015-22
Britt, W; Fay, J; Seals, J et al. (1995) Formulation of an immunogenic human cytomegalovirus vaccine: responses in mice. J Infect Dis 171:18-25
Britt, W J; Harrison, C (1994) Identification of an abundant disulfide-linked complex of glycoproteins in the envelope of guinea pig cytomegalovirus. Virology 201:294-302

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