Rift Valley Fever Virus: Molecular Biologic Studies of the M Segment RNA (Ribonucleic Acids) for Application in Disease Prevention

摘要

The mission of this contract was to elucidate the molecular and biologic properties of the middle (M) genomic segment of Rift Valley fever virus (RVFV), and the apply the new-found basic research information toward strategies for RVF disease prevention. The molecular characteristics of the M segment messenger RNA were prescribed, as were the gene products encoded therein. The single open reading frame within this RNA codes for four products: the two viral envelope glycoproteins G2 and G1, a glycosylated 78kd protein, and a nonglycosylated 14kd protein. The expression of the full complement of M segment-encoded proteins is complex and involves multiple translational initiation events giving rise to primary translation products which are co-translationally processed to yield the mature proteins. Portions of the RVFV M segment were engineered into bacterial expression systems for the production of subunit protein immunogens and into recombinant vaccinia viruses for creation of live virus vaccine candidates. The bacterial products were marginally immunogenic, capable of protecting only a portion of immunized laboratory animals from RVF. The glycoprotein G2 was found to be the essential and sufficient protective immunogen. Important immunologic determinants on this protein were mapped. These investigations have provided a great deal of insight into the molecular and immunologic properties of the M segment and its products. Keywords: Monoclonal antibodies; Rift Valley fever virus; M segment rna; Gene expression strategy; Recombinant dna; Subunit immunogens; Protective immunity; RAI. (kt)