The structure and replication of myxoviruses and paramyxoviruses will be investigated, with emphasis on correlation of the structure of the viral proteins with the mechanisms by which they exert their biological activities. Using virological, biochemical, and biophysical approaches we shall investigate the site of action of the paramyxovirus F glycoprotein, and the mechanism by which it induces the membrane fusion that is involved in virus penetration, cell fusion, and hemolysis. The site and mechanism of action of oligopeptides which specifically inhibit the activities of the paramyxovirus F protein or the myxovirus HA glycoprotein will be determined, and the efficacy of these oligopeptides in inhibiting viral replication in animals evaluated. The immunogenicity of purified viral glycoproteins, alone or reconstituted with lipids into membranes, will be evaluated with regard to their eventual use in vaccines. The primary structure of the paramyxovirus HN protein will be determined, and the identification of the receptor-binding site on the influenza virus HA protein will be attempted using variants of A/H3N2 virus which differ at that site. The structure of the paramyxovirus nucleocapsid and its associated proteins, and the effects of salt concentration and proteolytic cleavage of the NP subunits on the helical conformation of the nucleocapsid will be studied. The recently discovered over-lapping genes on RNA segment 8 of influenza virus and their gene products (NS1 and NS2) will be characterized, and the possibility that two proteins (M1 and M2) are coded by over-lapping genes on RNA segment 7 of influenza viruses will be explored. The level of the defect (i.e., in transcription or translation) in synthesis of the M protein of measles virus in brain cells of patients with subacute sclerosing panencephalitis (SSPE) will be investigated. The role of actin and 10 nm filments in virus assembly and certain cellular processes will be investigated using labeled probes for viral and cytoskeletal components and inhibitors of cytoskeletal function.
