Bunyamwera Bunyavirus Nonstructural Protein NSs is a Nonessential Gene Product That Contributes to Viral Pathogenesis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 2; pp. 664 - 669
• Main Authors: Bridgen, Anne, Weber, Friedemann, Fazakerley, John K., Elliott, Richard M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16.01.2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Aedes - cytology; Amino Acid Sequence; Animals; Base Sequence; Biological Sciences; Brain - virology; Bunyamwera virus; Bunyamwera virus - genetics; Bunyamwera virus - pathogenicity; Bunyaviridae; Bunyaviridae Infections - virology; Bunyavirus; Cell Line; Cricetinae; Defective Viruses - genetics; Defective Viruses - pathogenicity; Embryo, Mammalian - cytology; Embryo, Nonmammalian; Female; Gene Deletion; Gene Expression Regulation, Viral; Genes, Overlapping; Genes, Reporter; Genetics; Genomes; Infections; Interferon; Interferon-beta - biosynthesis; Interferon-beta - genetics; Kidney - cytology; Mesocricetus; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Neurons; NSs protein; Nucleocapsid - genetics; nucleocapsid protein; Nucleocapsid Proteins; Orthobunyavirus; Plasmids; Promoter Regions, Genetic; Protein Biosynthesis; Protein synthesis; Proteins; Recombinant Fusion Proteins - biosynthesis; Ribonucleic acid; RNA; RNA, Viral - genetics; Specific Pathogen-Free Organisms; Transfection; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - physiology; Virology; Virulence - genetics; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.98.2.664

Bunyamwera virus (family Bunyaviridae, genus Bunyavirus) contains a tripartite negative-sense RNA genome. The smallest RNA segment, S, encodes the nucleocapsid protein N and a nonstructural protein, NSs, in overlapping reading frames. We have generated a mutant virus lacking NSs, called BUNdelNSs, by reverse genetics. Compared with the wild-type (wt) virus, BUNdelNSs exhibited a smaller plaque size and generated titers of virus approximately 1 log lower. In mammalian cells, the mutant expressed greatly increased levels of N protein; significantly, the marked inhibition of host cell protein synthesis shown by wt virus was considerably impaired by BUNdelNSs. When inoculated by the intracerebral route BUNdelNSs killed BALB/c mice with a slower time course than wt and exhibited a reduced cell-to-cell spread, and titers of virus in the brain were lower. In addition, the abrogation of NSs expression changed Bunyamwera virus from a noninducer to an inducer of an interferon-β promoter. These results suggest that, although not essential for growth in tissue culture or in mice, the bunyavirus NSs protein has several functions in the virus life cycle and contributes to viral pathogenesis.