Abstract

The proposed research will focus on parainfluenza virus assembly by studying protein-protein interactions between the viral nucleocapsid, matrix protein, and the viral envelope glycoproteins.
Aim 1 will determine the protein-protein interactions that are responsible for the incorporation of the hemagglutinin-neuraminidase (HN) into infectious virus particles, and will use site-directed mutagenesis to identify critical amino acid residues of the cytoplasmic tail of HN that interact with the nucleocapsid to allow incorporation of HN into the viral envelope.
Aim 2 will determine the mechanism of nucleocapsid incorporation into virus particles. Nucleocapsids composed of Sendai and human parainfluenza virus type 1 chimeric NP molecules will be expressed and the domains and specific residues of NP that are critical for assembly into the virus envelope will be elucidated.
Aim 3 proposes to study the structure/function relationship of the matrix protein of parainfluenza viruses. Sendai virus temperature-sensitive (ts) matrix mutants can be complemented with a cDNA-expressed wild type M protein. Mutagenesis of the (complementing) protein may allow the defining of functional domains.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI011949-26
Application #
6372956
Study Section
Virology Study Section (VR)
Program Officer
Rubin, Fran A
Project Start
1978-07-01
Project End
2004-03-31
Budget Start
2001-04-01
Budget End
2004-03-31
Support Year
26
Fiscal Year
2001
Total Cost
$260,700
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

Hurwitz, Julia L (2008) Development of recombinant Sendai virus vaccines for prevention of human parainfluenza and respiratory syncytial virus infections. Pediatr Infect Dis J 27:S126-8
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
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
Coronel, E C; Takimoto, T; Murti, K G et al. (2001) Nucleocapsid incorporation into parainfluenza virus is regulated by specific interaction with matrix protein. J Virol 75:1117-23
Suzuki, T; Portner, A; Scroggs, R A et al. (2001) Receptor specificities of human respiroviruses. J Virol 75:4604-13
Bousse, T; Takimoto, T; Matrosovich, T et al. (2001) Two regions of the P protein are required to be active with the L protein for human parainfluenza virus type 1 RNA polymerase activity. Virology 283:306-14
Takimoto, T; Taylor, G L; Crennell, S J et al. (2000) Crystallization of Newcastle disease virus hemagglutinin-neuraminidase glycoprotein. Virology 270:208-14

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