The development of a reverse genetics system for influenza viruses allows us to site-specifically mutate the genomes of these negative strand RNA viruses. Thus, we are now able to perform structure-function studies on proteins in the context of infectious virus and to define specific virulence characteristics on a molecular level. Using mutational analysis, we will study the functional and antigenic determinants of the influenza virus neuraminidase (NA) in the cytoplasmic tail, the stalk and the head region. The characterization of genetically manipulated influenza viruses (transfectants) will define in a more precise way how the NA influences host range or neurovirulence. Similar studies will be done on the hemagglutinin (HA) in order to define the role of palmitoylation of the HA in the formation of infectious particles and to study host range and virulence as it is influenced by the HA. In order to facilitate the rapid isolation of transfectants with changes in non- HA/non-NA genes, attempts will be made to develop convenient systems which will allow for the rapid exchange of any influenza virus gene with a cDNA-derived RNA segment. We will also develop protocols to establish a reverse genetics system for influenza B viruses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI011823-24
Application #
2330309
Study Section
Experimental Virology Study Section (EVR)
Project Start
1977-05-01
Project End
1999-01-31
Budget Start
1997-02-01
Budget End
1998-01-31
Support Year
24
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Durbin, J E; Fernandez-Sesma, A; Lee, C K et al. (2000) Type I IFN modulates innate and specific antiviral immunity. J Immunol 164:4220-8
O'Neill, R E; Talon, J; Palese, P (1998) The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J 17:288-96
Rodrigues, M; Li, S; Murata, K et al. (1994) Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes. Comparison of their immunogenicity and capacity to induce protective immunity. J Immunol 153:4636-48
Li, S; Rodrigues, M; Rodriguez, D et al. (1993) Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. Proc Natl Acad Sci U S A 90:5214-8
Luo, G; Palese, P (1992) Genetic analysis of influenza virus. Curr Opin Genet Dev 2:77-81
Luo, G; Bergmann, M; Garcia-Sastre, A et al. (1992) Mechanism of attenuation of a chimeric influenza A/B transfectant virus. J Virol 66:4679-85
Bergmann, M; Garcia-Sastre, A; Palese, P (1992) Transfection-mediated recombination of influenza A virus. J Virol 66:7576-80
Lin, D A; Roychoudhury, S; Palese, P et al. (1991) Evolutionary relatedness of the predicted gene product of RNA segment 2 of the tick-borne Dhori virus and the PB1 polymerase gene of influenza viruses. Virology 182:1-7
Enami, M; Sharma, G; Benham, C et al. (1991) An influenza virus containing nine different RNA segments. Virology 185:291-8
Luo, G X; Luytjes, W; Enami, M et al. (1991) The polyadenylation signal of influenza virus RNA involves a stretch of uridines followed by the RNA duplex of the panhandle structure. J Virol 65:2861-7

Showing the most recent 10 out of 38 publications