Abstract

The goal of this project is to analyze the structure and function of arenaviruses at the molecular and antigenic level. Specific objectives include a detailed structural and antigenic analysis of the glycoproteins of LCM and Pichinde viruses in order to understand the assembly and diversity of these molecules. Analysis of persistent arenavirus infections will be directed toward determining the repertoire of immune responses to mice against persisting virus, and studying the changes that virus undergoes in the course of persistent disease. Molecular biology of the arenaviruses will be approached in two ways. First, we will study the structure and functions of gene products encoded on the 8-9 kb L RNA segment. Second, we will undertake molecular cloning of the Tacaribe virus, a virus which differs in fundamental biological and structural features from LCM and Pichinde viruses, in order to begin to understand the molecular basis for these differences. Arenaviruses are significant human pathogens on the African and South American continents. In addition, Lymphocytic Choriomeningitis virus has proven to be an extremely valuable and instructive laboratory model. The studies described in this application will provide basic information to interpret the biology, structure and evolution of the arenaviruses and will suggest rational strategies of diagnosis, therapy and prevention of arenavirus diseases of man.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI016102-11
Application #
3126565
Study Section
Experimental Virology Study Section (EVR)
Project Start
1979-08-01
Project End
1991-07-31
Budget Start
1989-08-01
Budget End
1991-07-31
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Baldridge, J R; McGraw, T S; Paoletti, A et al. (1997) Antibody prevents the establishment of persistent arenavirus infection in synergy with endogenous T cells. J Virol 71:755-8
Pearce, B D; Steffensen, S C; Paoletti, A D et al. (1996) Persistent dentate granule cell hyperexcitability after neonatal infection with lymphocytic choriomeningitis virus. J Neurosci 16:220-8
Di Simone, C; Buchmeier, M J (1995) Kinetics and pH dependence of acid-induced structural changes in the lymphocytic choriomeningitis virus glycoprotein complex. Virology 209:3-9
Baldridge, J R; Pearce, B D; Parekh, B S et al. (1993) Teratogenic effects of neonatal arenavirus infection on the developing rat cerebellum are abrogated by passive immunotherapy. Virology 197:669-77
Baldridge, J R; Buchmeier, M J (1992) Mechanisms of antibody-mediated protection against lymphocytic choriomeningitis virus infection: mother-to-baby transfer of humoral protection. J Virol 66:4252-7
Burns, J W; Buchmeier, M J (1991) Protein-protein interactions in lymphocytic choriomeningitis virus. Virology 183:620-9
Fazakerley, J K; Southern, P; Bloom, F et al. (1991) High resolution in situ hybridization to determine the cellular distribution of lymphocytic choriomeningitis virus RNA in the tissues of persistently infected mice: relevance to arenavirus disease and mechanisms of viral persistence. J Gen Virol 72 ( Pt 7):1611-25
Wright, K E; Buchmeier, M J (1991) Antiviral antibodies attenuate T-cell-mediated immunopathology following acute lymphocytic choriomeningitis virus infection. J Virol 65:3001-6
Wright, K E; Spiro, R C; Burns, J W et al. (1990) Post-translational processing of the glycoproteins of lymphocytic choriomeningitis virus. Virology 177:175-83
Wright, K E; Salvato, M S; Buchmeier, M J (1989) Neutralizing epitopes of lymphocytic choriomeningitis virus are conformational and require both glycosylation and disulfide bonds for expression. Virology 171:417-26

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