Hantaan virus was discovered only ten years ago, and since then has become the focus of much interest in the medical community, because of its world-wide distribution. We have cloned into expression systems the genes for the structural proteins of the virus and intend to use these clones in exploration of the functional aspects of this fascinating virus. First, several features of the structure of Hantaan glycoproteins will be investigated, including modes of synthesis and processing, the nature of the oligosaccharide residues, and the sites of glycosylation. Possible disulfide bonding will be examined and the likely association of glycoproteins into higher order structures probed. The role of these proteins in cell fusion, in infectivity and in recognition of a cellular receptor for the virus will be investigated. New constructs in eukaryotic expression systems will be made, which will include intact and mutagenised versions of the genes for structural proteins; these will be used in a variety of assays for function, including cellular localization, identification of signal and membrane anchor sequences, and cleavage sites. The many likely functions of the nucleocapsid protein, N, will be assessed. Functions include RNA-binding, self-association and association with glycoproteins. The immune responses to virus proteins will be measured, revealing immunoreactive domains responsible both for a humoral response and for cell-mediated immunity. These studies are expected to lead to a new understanding of Hantaan virus replication and to have important implications for virus pathogenesis, as well as antiviral therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI025376-06
Application #
2062968
Study Section
Experimental Virology Study Section (EVR)
Project Start
1989-03-01
Project End
1995-02-28
Budget Start
1993-03-01
Budget End
1995-02-28
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
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Pensiero, M N; Sharefkin, J B; Dieffenbach, C W et al. (1992) Hantaan virus infection of human endothelial cells. J Virol 66:5929-36
Hay, J; Ruyechan, W T (1992) Regulation of herpes simplex virus type 1 gene expression. Curr Top Microbiol Immunol 179:1-14
Pensiero, M N; Dveksler, G S; Cardellichio, C B et al. (1992) Binding of the coronavirus mouse hepatitis virus A59 to its receptor expressed from a recombinant vaccinia virus depends on posttranslational processing of the receptor glycoprotein. J Virol 66:4028-39