Amino acid mutations in the replicase protein nsP3 of Semliki Forest virus cumulatively affect neurovirulence

The Journal of General Virology
M T Tuittila, A E Hinkkanen

Abstract

It has been shown previously that an avirulent Semliki Forest virus (SFV) clone, rA774, engineered to carry the nsP3 gene of the virulent clone SFV4 becomes highly neurovirulent and is lethal for adult BALB/c mice. rA774, like several other alphaviruses, has an opal termination codon close to the 5' end of nsP3 (aa 469), while SFV4 has an arginine residue at this position. Mutation of the opal codon to an arginine residue increases the virulence of rA774 but does not reconstruct the severe neurovirulence of SFV4. Additionally, nsP3 amino acid sequences differ between these two strains by eight amino acids and by a deletion of seven amino acids in the C-terminal third of rA774 nsP3. This study shows that neurovirulence can be reconstituted gradually by exchanging individual amino acids and is fully retained when combinations of two nsP3 mutations, V(11)-->I and L(201)-->F, V(11)-->I and D(249)-->N, A(48)-->E and G(70)-->A or T(435)-->A and F(442)-->L, are introduced into an rA774 derivative carrying R(469). The critical role of the arginine codon for neurovirulence was confirmed further by the acquisition of a fully lethal phenotype following the introduction of R(469) into a moderately virulent rA774 recombinant carrying the SF...Continue Reading

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Citations

Feb 12, 2008·Virus Genes·Christopher H LogueGregory J Atkins
Dec 18, 2009·Journal of Virology·Margus VarjakAndres Merits
Dec 3, 2003·Journal of Virology·Indra DéDorothea L Sawicki
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Oct 17, 2018·Proceedings of the National Academy of Sciences of the United States of America·Rachy AbrahamDiane E Griffin
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Jun 8, 2007·The Journal of General Virology·Stefan A Deuber, Jovan Pavlovic
Aug 29, 2021·Pathogens·Margarita V Rangel, Kenneth A Stapleford

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