Abstract

Project 3, The 1918 HA and NA: Antigens and Virulence Factors, seeks to use a combination of reverse genetics, molecular biological, biochemical and serological assays to further our understanding of the contributions at the molecular level, of the HA and NA proteins of the 1918 virus in virulence, and to assess the antigenic novelty of the 1918 surface glycoproteins. Preliminary data suggest that the 1918 HA and NA confer a high virulence phenotype upon influenza viruses in mice Tumpey, et al. (2002) PNAS 99, 13849-54. This project will evaluate the hypothesis that the high mortality rate of the 1918 pandemic was influenced both by the existence of an immunologically naive human population and by additional properties of the 1918 virus HA and NA. Pathogenesis studies of recombinant viruses containing 1918 HA and NA genes will be conducted in mice and chickens and will further evaluate the role of these proteins in virulence. In addition, Dr. Basler's laboratory will be reconstructing genes of the 1918 genes according to the sequences generated by Dr. Taubenberger. These reconstructed genes will be used by the different projects of the program project.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI058113-03
Application #
7268896
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
3
Fiscal Year
2006
Total Cost
$217,918
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Orgel, Kelly A; Duan, Shiteng; Wright, Benjamin L et al. (2017) Exploiting CD22 on antigen-specific B cells to prevent allergy to the major peanut allergen Ara h 2. J Allergy Clin Immunol 139:366-369.e2
Rivera, Andrea; Barr, Tasha; Rais, Maham et al. (2016) microRNAs Regulate Host Immune Response and Pathogenesis During Influenza Infection in Rhesus Macaques. Viral Immunol 29:212-27
McBride, Ryan; Paulson, James C; de Vries, Robert P (2016) A Miniaturized Glycan Microarray Assay for Assessing Avidity and Specificity of Influenza A Virus Hemagglutinins. J Vis Exp :
Cheng, Chu-Wen; Chou, Chi-Chi; Hsieh, Hsiao-Wu et al. (2015) Efficient Mapping of Sulfated Glycotopes by Negative Ion Mode nanoLC-MS/MS-Based Sulfoglycomic Analysis of Permethylated Glycans. Anal Chem 87:6380-8
Yoon, Sun-Woo; Chen, Noam; Ducatez, Mariette F et al. (2015) Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus. Sci Rep 5:12828
Riegger, David; Hai, Rong; Dornfeld, Dominik et al. (2015) The nucleoprotein of newly emerged H7N9 influenza A virus harbors a unique motif conferring resistance to antiviral human MxA. J Virol 89:2241-52
de Vries, Robert P; Zhu, Xueyong; McBride, Ryan et al. (2014) Hemagglutinin receptor specificity and structural analyses of respiratory droplet-transmissible H5N1 viruses. J Virol 88:768-73
Dreyfus, Cyrille; Ekiert, Damian C; Wilson, Ian A (2013) Structure of a classical broadly neutralizing stem antibody in complex with a pandemic H2 influenza virus hemagglutinin. J Virol 87:7149-54
de Vries, Robert P; de Vries, Erik; Martínez-Romero, Carles et al. (2013) Evolution of the hemagglutinin protein of the new pandemic H1N1 influenza virus: maintaining optimal receptor binding by compensatory substitutions. J Virol 87:13868-77
Zhu, Xueyong; Guo, Yong-Hui; Jiang, Tao et al. (2013) A unique and conserved neutralization epitope in H5N1 influenza viruses identified by an antibody against the A/Goose/Guangdong/1/96 hemagglutinin. J Virol 87:12619-35

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