Abstract

Paramyxoviruses are the most important cause of respiratory disease in children. The long-term objectives of our research are to develop means to prevent respiratory disease caused by parainfluenza viruses (PIV). To reach that objective, the proposed research will focus on establishing the three- dimensional structure (3D) of the paramyxovirus HN protein using x-ray crystallography. The role of this protein in virus attachment, penetration, virus spread, and as a major neutralizing antigen makes the structure important for vaccine and drug development. Using a reverse genetics, this proposal also addresses the determinants of PIV host range and tissue tropism. Using genetic and biochemical approaches aims 3 explores the unknown mechanism of PIV budding, a potential target for drug intervention.
The specific aims of this proposal are 1) Proposal: Establish a high-resolution 3D structure of HN. 2) Question: What are the virus specific determinants of parainfluenza host range and tissue tropism? 3) Proposal: determine the mechanism of virus budding induced by paramyxovirus membrane proteins. The studies proposed in these aims, HN structure, virus release (budding), and virus spread (host range determinants) are potential intervention targets in the infectious cycle.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI038956-07
Application #
6626515
Study Section
Virology Study Section (VR)
Program Officer
Rubin, Fran A
Project Start
1997-01-01
Project End
2004-12-31
Budget Start
2003-01-01
Budget End
2003-12-31
Support Year
7
Fiscal Year
2003
Total Cost
$182,682
Indirect Cost

  Institution

Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105

  Publications

Krishnamurthy, Sateesh; Takimoto, Toru; Scroggs, Ruth Ann et al. (2006) Differentially regulated interferon response determines the outcome of Newcastle disease virus infection in normal and tumor cell lines. J Virol 80:5145-55
Alymova, Irina V; Portner, Allen; Takimoto, Toru et al. (2005) The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae. Antimicrob Agents Chemother 49:398-405
Zaitsev, Viatcheslav; von Itzstein, Mark; Groves, Darrin et al. (2004) Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion. J Virol 78:3733-41
Bousse, Tatiana L; Taylor, Garry; Krishnamurthy, Sateesh et al. (2004) Biological significance of the second receptor binding site of Newcastle disease virus hemagglutinin-neuraminidase protein. J Virol 78:13351-5
Takimoto, Toru; Portner, Allen (2004) Molecular mechanism of paramyxovirus budding. Virus Res 106:133-45
Connaris, Helen; Takimoto, Toru; Russell, Rupert et al. (2002) Probing the sialic acid binding site of the hemagglutinin-neuraminidase of Newcastle disease virus: identification of key amino acids involved in cell binding, catalysis, and fusion. J Virol 76:1816-24
Takimoto, Toru; Taylor, Garry L; Connaris, Helen C et al. (2002) Role of the hemagglutinin-neuraminidase protein in the mechanism of paramyxovirus-cell membrane fusion. J Virol 76:13028-33
Bousse, Tatiana; Matrosovich, Tatyana; Portner, Allen et al. (2002) The long noncoding region of the human parainfluenza virus type 1 f gene contributes to the read-through transcription at the m-f gene junction. J Virol 76:8244-51
Takimoto, T; Murti, K G; Bousse, T et al. (2001) Role of matrix and fusion proteins in budding of Sendai virus. J Virol 75:11384-91
Suzuki, T; Portner, A; Scroggs, R A et al. (2001) Receptor specificities of human respiroviruses. J Virol 75:4604-13

Showing the most recent 10 out of 13 publications