PMID:11209062

Citation	Bridgen, A, Weber, F, Fazakerley, JK and Elliott, RM (2001) Bunyamwera bunyavirus nonstructural protein NSs is a nonessential gene product that contributes to viral pathogenesis. Proc. Natl. Acad. Sci. U.S.A. 98:664-9
Abstract	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-beta 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.
Links	PubMed PMC14645 Online version:10.1073/pnas.98.2.664
Keywords	Aedes/cytology; Amino Acid Sequence; Animals; Base Sequence; Brain/virology; Bunyamwera virus/genetics; Bunyamwera virus/pathogenicity; Bunyaviridae Infections/virology; 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; Interferon-beta/biosynthesis; Interferon-beta/genetics; Kidney/cytology; Mesocricetus; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Nucleocapsid/genetics; Nucleocapsid Proteins; Promoter Regions, Genetic; Protein Biosynthesis; RNA, Viral/genetics; Recombinant Fusion Proteins/biosynthesis; Specific Pathogen-Free Organisms; Transfection; Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/physiology; Virulence/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
BUNYW:NSS	involved_in	GO:0046725: negative regulation by virus of viral protein levels in host cell	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
BUNYW:NSS	involved_in	GO:0009405: pathogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
BUNYW:NSS		GO:0046725: negative regulation of viral protein levels in host cell	ECO:0000315:		P		Fig 4A: BHK cells were infected with wildtype BUN, Maguari virus, or BUNdelNSs, N proteins appeared more prominently in cells infected with BUNdelNSs	complete CACAO 9701
BUNYW:NSS		GO:0017148: negative regulation of translation	ECO:0000315:		P		Fig 4A: BHK cells were infected with wildtype BUN, Maguari virus, or BUNdelNSs, N proteins appeared more prominently in cells infected with BUNdelNSs	complete CACAO 9702
BUNYW:NSS		GO:0010629: negative regulation of gene expression	ECO:0000315:		P		Fig 4A: BHK cells were infected with wildtype BUN, Maguari virus, or BUNdelNSs, N proteins appeared more prominently in cells infected with BUNdelNSs	complete CACAO 9703
BUNYW:NSS		GO:0009405: pathogenesis	ECO:0000315:		P		Fig. 5: mice were inoculated with wildtype or BUNdelNSs, mice inoculated with BUNdelNSs took longer to die than mice inoculated with wildtype	complete CACAO 9704
BUNYW:NSS		GO:0039501: suppression by virus of host type I interferon production	ECO:0000315:		P		Fig. 7A: BF cells were infected with wildtype or mutant virus, wildtype virus resulted in decreased luciferase activity compared to mutant (luciferase activity related to induction of IFN-beta promoter) Fig. 7B: to make sure NSs targeted IFN-beta and not just proteins in general, cells were transfected with a plasmid where luciferase expression was controlled by a different promoter, luciferase activity of the wild-type and mutant were similar and higher than luficerase activity of the wild-type in Fig. 7A	complete CACAO 9705
BUNYW:NSS		GO:0039657: suppression by virus of host gene expression	ECO:0000315:		P		Fig. 4B: BHK cells were infected with wildtype, and mutant. More host cells proteins were seen in cells infected by mutant than cells infected by wildtype	complete CACAO 9708
BUNYW:NSS		GO:0039604: suppression by virus of host translation	ECO:0000315:		P		Fig. 4B: BHK cells were infected with wildtype or BUNdelNSs, more host cell proteins were seen in cells infected with mutant than cells infected with wildtype	complete CACAO 9710
BUNYW:NSS		GO:0039653: suppression by virus of host transcription	ECO:0000315:		P		Fig. 4B: BHK cells were infected with wildtype, and mutant. More host cells proteins were seen in cells infected by mutant than cells infected by wildtype	complete CACAO 9711
BUNYW:NSS		GO:0019080: viral gene expression	ECO:0000315:		P		Fig 4A: BHK cells were infected with wildtype BUN, Maguari virus, or BUNdelNSs, N proteins appeared more prominently in cells infected with BUNdelNSs	complete CACAO 9713
BUNYW:NSS		GO:0019081: viral translation	ECO:0000315:		P		Fig 4A: BHK cells were infected with wildtype BUN, Maguari virus, or BUNdelNSs, N proteins appeared more prominently in cells infected with BUNdelNSs	complete CACAO 9714
BUNYW:NSS		GO:0019083: viral transcription	ECO:0000315:		P		Fig 4A: BHK cells were infected with wildtype BUN, Maguari virus, or BUNdelNSs, N proteins appeared more prominently in cells infected with BUNdelNSs	complete CACAO 9718
BUNYW:NSS	involved_in	GO:0039501: suppression by virus of host type I interferon production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
BUNYW:NSS	involved_in	GO:0039657: suppression by virus of host gene expression	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
BUNYW:NSS	involved_in	GO:0019080: viral gene expression	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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