Deletions in the hypervariable domain of the nsP3 gene attenuate Semliki Forest virus virulence

The Journal of General Virology
Sareen E GalbraithGregory J Atkins

Abstract

Major virulence determinants of Semliki Forest virus (SFV) lie within the non-structural genes that form the replicase complex proteins. Gene exchange between virulent and avirulent viruses has shown that the nsP3 gene, which has essential 5' conserved domains and a non-essential hypervariable 3' domain, is one of the virulence determinants. This protein plays a role in subgenomic 26S and negative-strand RNA synthesis and is thought to function with nsP1 to anchor replication complexes to cell membrane structures. Studies to date have focused on analysing the effect of mutational changes spread over the whole gene on virulence of the virus. The virulent SFV4 virus, derived from an infectious clone, was utilized to analyse the effect on virulence of large deletions in the hypervariable domain of nsP3. Two viruses with different in-frame deletions that spanned this domain showed reduced rates of RNA synthesis and multiplication in cell culture. In adult BALB/c mice, these viruses were avirulent after intramuscular and intraperitoneal inoculation, and brains sampled from infected mice showed minimal or no evidence of pathology. These deleted viruses had greatly reduced virulence when administered by the intranasal route and brains...Continue Reading

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Citations

Nov 13, 2008·Expert Reviews in Molecular Medicine·Gregory J AtkinsBrian J Sheahan
Dec 18, 2009·Journal of Virology·Margus VarjakAndres Merits
Jan 30, 2013·PLoS Neglected Tropical Diseases·Kali D Saxton-ShawAnn M Powers
Jul 30, 2015·The Journal of General Virology·Jonathan C RuppRichard W Hardy
Mar 31, 2016·The Journal of General Virology·Gregory J Atkins, Brian J Sheahan
Dec 29, 2013·Journal of Virology·David HallengärdPeter Liljeström
Mar 14, 2014·Journal of Virology·Marc D PanasGerald M McInerney
Mar 27, 2019·Viruses·Kelli L Barr, Vedana Vaidhyanathan
Jan 30, 2018·Frontiers in Microbiology·Tyler LarkAarthi Narayanan

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