Abstract

We will attempt to (1) permanently express different influenza A virus genes (gene complexes) in eukaryotic cells via bovine papilloma virus vectors. This system will allow us to study the functional interaction of viral proteins and to establish an effective complementation system for the isolation of novel influenza A virus mutants. A major effort will be directed towards (2) rescuing cloned viral cDNA into infectious virus. This approach would allow--for the first time--site-specific alterations in the genome of a negative strand RNA virus and the generation of specific mutants including those to be used as viral vaccine strains. We also plan to (3) explore the nucleophilic signals of the influenza A NS1 and NS2 proteins in order to arrive at an understanding of the requirements necessary for intracellular migration of these proteins. We will (4) continue structural work on influenza virus genes and plan to clone and sequence the remaining genes of an influenza C virus. Finally, (5) work will continue with respect to the precise measurements of mutation rates of influenza A, B and C viruses, and we hope to compare these values with that obtained for an RNA tumor virus. These studies should allow us to compare a fundamental genetic property among different virus classes and to correlate error rate of viral polymerases with variability of viruses in nature.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018998-18
Application #
2886415
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Lambert, Linda C
Project Start
1982-05-01
Project End
2002-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
18
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

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

  Publications

Park, Man-Seong; Steel, John; Garcia-Sastre, Adolfo et al. (2006) Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease. Proc Natl Acad Sci U S A 103:8203-8
Lowen, Anice C; Mubareka, Samira; Tumpey, Terrence M et al. (2006) The guinea pig as a transmission model for human influenza viruses. Proc Natl Acad Sci U S A 103:9988-92
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
O'Neill, R E; Jaskunas, R; Blobel, G et al. (1995) Nuclear import of influenza virus RNA can be mediated by viral nucleoprotein and transport factors required for protein import. J Biol Chem 270:22701-4
Piccone, M E; Fernandez-Sesma, A; Palese, P (1993) Mutational analysis of the influenza virus vRNA promoter. Virus Res 28:99-112
Li, X; Palese, P (1992) Mutational analysis of the promoter required for influenza virus virion RNA synthesis. J Virol 66:4331-8
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

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