Influenza viruses are important human pathogens whose interactions with the infected host are complex. Since these negative strand RNA viruses possess a nuclear phase during their replication cycle, the intracellular trafficking of the viral components involves the hijacking and use of much of the host cell's transport machinery. Specifically, Aim 1 of the proposal is designed to elucidate the mechanism and the cellular transport requirements for the nuclear import of the influenza virus ribonucleoprotein (RNP). Following amplification of the incoming viral RNA in the nucleus, the newly synthesized RNA must exit into the cytoplasm.
In Aim 2 we will ask how the viral nuclear export protein (NEP) interacts with the cellular export proteins and how the viral NEP adapter interacts with the viral nucleoprotein complex. Finally, we postulate (Aim 3) that the influenza virus Ml protein has a specific budding domain which allows recruiting of the host's budding machinery, and thus drives the assembly of viral particles in the cytoplasmic membrane. Our approaches to explore the mechanisms of virus-host interactions will take advantage of our improved reverse genetics technologies to construct influenza virus mutants and of recent advances in analyzing the functions of cellular proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018998-23
Application #
6744038
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Lacourciere, Karen A
Project Start
1982-05-01
Project End
2007-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
23
Fiscal Year
2004
Total Cost
$423,750
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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
Muster, T; Subbarao, E K; Enami, M et al. (1991) An influenza A virus containing influenza B virus 5' and 3' noncoding regions on the neuraminidase gene is attenuated in mice. Proc Natl Acad Sci U S A 88:5177-81

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