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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Virology Study Section (VR)
Program Officer
Rubin, Fran A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
St. Jude Children's Research Hospital
United States
Zip Code
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

Showing the most recent 10 out of 48 publications