A single amino acid change in the E2 spike protein of a virulent strain of Semliki Forest virus attenuates pathogenicity

• Published in: Journal of general virology Vol. 75; no. 3; pp. 663 - 668
• Main Authors: Glasgow, Gwendoline M, Killen, Helen M, Liljestrom, Peter, Sheahan, Brian J, Atkins, Gregory J
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.03.1994; Society for General Microbiology
• Subjects: Alphavirus Infections - microbiology; Amino Acids; Animals; Base Sequence; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Mice; Microbiology; Molecular Sequence Data; Mutagenesis, Site-Directed; Pregnancy; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Semliki Forest virus; Semliki forest virus - genetics; Semliki forest virus - pathogenicity; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - physiology; Virology; Virulence - genetics; Semliki forest virus; Togaviridae; Spicule; Virus; Pathogenicity; Proteins; Avirulent strain; Substitution; Virulent strain; Alphavirus; Property structure relationship; Mutation; Virus envelope
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-75-3-663

1 Department of Microbiology, Moyne Institute, Trinity College, Dublin 2, Ireland, 2 Department of Molecular Biology, Karolinska Institute, S-141 57 Huddinge, Sweden and 3 Department of Veterinary Pathology, Faculty of Veterinary Medicine, University College Dublin, Ballsbridge, Dublin 4, Ireland The virulent strain SFV4 of Semliki Forest virus (SFV), produced from the infectious clone pSP6-SFV4, is lethal after intranasal (i.n.) infection of adult mice and for pregnant mice after intraperitoneal (i.p.) infection. In contrast, the A7 strain of SFV is avirulent when given i.n. to adult mice, but induces fetal death in pregnant mice after i.p. infection. The nucleotide and deduced amino acid sequences of part of the core and all of the envelope region of A7-SFV were determined and compared to those of SFV4. A7 differed from SFV4 at 80 nucleotides (nt) in the coding sequence, 15 of which were associated with amino acid differences and seven of which (two in the E2 protein and five in E1) were non-conservative. The 3' non-coding sequence of A7 was longer (415 nt) than that of SFV4 (263 nt) and a divergent sequence of 181 nt was present adjacent to the end of the E1 coding region. The effects on virulence of two mutations in the E2 gene of SFV4, resulting in the non-conservative amino acid substitutions present in A7, were analysed. One mutation (mut 8729 a/c) resulted in only slight attenuation, whereas the other (mut 8902 a/g) resulted in avirulence for pregnant mice. However, mut 8902 a/g was lethal for the majority of developing fetuses after i.p. infection of the mother. Received 3 September 1993; accepted 29 October 1993.