Creation of a Recombinant Rift Valley Fever Virus with a Two-Segmented Genome

Benjamin Brennan, Stephen R. Welch, Angela McLees, Richard M. Elliott

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Rift Valley fever virus (RVFV; family Bunyaviridae) is a clinically important, mosquito-borne pathogen of both livestock and humans, which is found mainly in sub-Saharan Africa and the Arabian Peninsula. RVFV has a trisegmented single-stranded RNA (ssRNA) genome. The L and M segments are negative sense and encode the L protein (viral polymerase) on the L segment and the virion glycoproteins Gn and Gc as well as two other proteins, NSm and 78K, on the M segment. The S segment uses an ambisense coding strategy to express the nucleocapsid protein, N, and the nonstructural protein, NSs. Both the NSs and NSm proteins are dispensable for virus growth in tissue culture. Using reverse genetics, we generated a recombinant virus, designated r2segMP12, containing a two-segmented genome in which the NSs coding sequence was replaced with that for the Gn and Gc precursor. Thus, r2segMP12 lacks an M segment, and although it was attenuated in comparison to the three-segmented parental virus in both mammalian and insect cell cultures, it was genetically stable over multiple passages. We further show that the virus can stably maintain an M-like RNA segment encoding the enhanced green fluorescent protein gene. The implications of these findings for RVFV genome packaging and the potential to develop multivalent live-attenuated vaccines are discussed.

Original languageEnglish
Pages (from-to)10310-10318
Number of pages9
JournalJournal of Virology
Volume85
Issue number19
Early online date27 Jul 2011
DOIs
Publication statusPublished - Oct 2011

Keywords

  • Rift Valley fever virus
  • DEFECTIVE INTERFERING PARTICLES
  • NONSTRUCTURAL PROTEIN NSS
  • NONCODING REGIONS
  • VIRAL-RNA
  • BUNYAVIRIDAE
  • REPLICATION
  • RESCUE
  • GENERATION
  • TRANSCRIPTION

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