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.
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