One of the goals of this application is to continue our studies on the genetic variation of influenza viruses in nature and their evolution in man and in animals. Specifically, we plan to analyze the nucleoprotein (NP) genes of human influenza A viruses isolated during a period of more than five decades. We will also study influenza A viruses (genes) from the avian and equine populations to determine their genetic stability relative to human strains. Also, a continuing molecular analysis of epidemiologically significant influenza A, B and C viruses is planned. Further goals concern the analysis of the receptor-binding/receptor-destroying activities of coronaviruses. Recently, we found that coronaviruses--like influenza C viruses-recognize O-acetylated sialic (neuraminic) acids as cell receptors and possess a sialate- O-acetylesterase as receptor-destroying enzyme. We now plan to clone the genes responsible for these activities in human coronavirus and we hope to identify the essential features of the catalytic and substrate binding sites in the proteins. We also plan to determine the mechanism of catalysis through the use of specific esterase substrates and esterase inhibitors. Compounds of the latter type may be effective in inhibiting virus replication and could represent a new approach to antiviral targeting with respect to viruses carrying an esterase (receptor-destroying) activity. We further plan to characterize the coronavirus receptors on permissive cells and we hope to determine whether (modified) sialic acids are the sole receptor molecules on target cells. Finally, we hope to explore the concept of receptor-binding and receptor-destroying activities in viruses belonging to other virus groups.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Experimental Virology Study Section (EVR)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mount Sinai School of Medicine
Schools of Medicine
New York
United States
Zip Code
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