Bunyamwera bunyavirus nonstructural protein NSs is a nonessential gene product that contributes to viral pathogenesis.

A Bridgen, F Weber, JK Fazakerley, Richard Michael Elliott

Research output: Contribution to journalArticlepeer-review

187 Citations (Scopus)

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 tacking 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 tower. 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.

Original languageEnglish
Pages (from-to)664-669
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number2
DOIs
Publication statusPublished - 16 Jan 2001

Keywords

  • reverse genetics
  • host cell shutoff
  • interferon antagonist
  • MESSENGER-RNA-SYNTHESIS
  • INFLUENZA-VIRUS
  • LA-CROSSE
  • TRANSLATIONAL REQUIREMENT
  • SENDAI-VIRUS
  • REPLICATION
  • POLYMERASE
  • ACTIVATION
  • VIRULENCE
  • SEGMENTS

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