The long term goals are to relate structure-function of influenza and paramyxoviruses, particularly the molecular biology of the pathogenesis of influenza and paramyxovirus infections.
The specific aim i s to identify the molecular basis of infectivity of Sendai virus, representative of paramyxoviruses. Host range mutants of Sendai virus have been isolated form a persistent infection of tissue cultures. The mutants will productively infect several continuous lines of tissue cultures whereas wild type Sendai virus will not. Since proteolytic cleavage of the fusion (F) protein is necessary for activating the infectivity, the F gene of wild type, host range mutants, and several stepwise revertants shall be sequenced. Additionally, the hemagglutinating-neuraminidase (HN) and matrix (M) genes shall be sequenced. One of the host range mutants has ts lesions in the HN and M genes, which provides us with a novel mutant to investigate the biological properties of the three envelope proteins (HN, F, & M) of Sendai virus. Sequencing will entail the molecular cloning of the cDNA of the three genes into pUC8 or pUC13, subcloned into phage M13 RF, and DNA sequencing carried out by the dideoxy method. By identifying the nucleotide sequences that may be responsible for infectivity, and from the predicted amino acid sequence at the cleavage/activation site of F protein in particular, this may provide a means to serve as a basis of ultimately to synthesize polypeptides for the possible treatment of paramyxovirus infections.
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