The structure and function of the genes of the paramyoxovirus SV5 will be investigated. The paramyoxovirus SV5 is a prototype of the paramyxovirus family of nonsegmented negative strand RNA viruses which includes Sendai virus, Newcastle disease virus, mumps virus, human parainfluenza virus types 1-5, the morbillivirus subgroups including measles virus and the pneumovirus subgroup including respiratory syncytial virus. We have recently synthesized complete cDNA copies of the SV5 mRNAs and these will be used to examine in detail the structure of the SV5 genome and their encoded proteins. We will search for a previously unrecognized mRNA and protein, designated SH, encoded on the genome between the F and HN genes. The predicted protein sequence derived from the SV5 genome nucleotide sequence indicates that SH has the properties expected for a membrane protein. We will obtain the nucleotide sequences between all the genes to investigate the possibility of further unrecognized genes. A careful analysis of the polycistronic mRNA species synthesized in infected cells and their ability to be translated will be done. We shall try to learn about the organization of the coding regions for polypeptides P and V which our available evidence suggests are synthesized by a bicistronic mRNA. The defect of the expression of the SV5 M gene in a macrophage derived cell line (P388D1) will be investigated, as this may mimic the replication pattern observed in paramyxovirus chronic and persistent infections. We shall investigate regions of the fusion protein necessary to cause cell fusion using the cloned F gene expressed in eukaryotic vectors, to learn how a viral protein mediates spread of infection. In addition, we will determine whether the N-terminal anchorage domain of the hemagglutinin-neuraminidase (HN) protein can anchor heterologous proteins in membranes, using recombinant DNA technology and eukaryotic expression vectors. We will also test the ability of the fusion protein and HN to induce antibody production in animals using the genes expressed in vaccinia virus recombinants to understand better the individual properties of these proteins with respect to their potential in vaccines.
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