title: A single nucleotide change in the E2 glycoprotein gene of Sindbis virus affects penetration rate in cell culture and virulence in neonatal mice.
abstract: The nucleotide sequence of the glycoprotein genes of fully virulent Sindbis virus and derived mutants that have reduced neurovirulence for neonatal mice (attenuated mutants) has been determined. A single amino acid difference, arginine instead of serine at position 114 of the mature E2 glycoprotein, distinguished the prototype attenuated mutant from its virulent wild-type parent. Virulent revertants of the attenuated mutant showed same-site reversion to the wild-type sequence. An identical single amino acid substitution, an arginine for the serine at E2 position 114, was found in a second independently selected attenuated mutant. The strains are characterized by genetic linkage between attenuation, accelerated penetration of baby hamster kidney cells, and efficient neutralization by the E2-specific monoclonal antibodies R6 and R13; selection for change in one property simultaneously selected for change in the other two (Olmsted, R. A., Baric, R. S., Sawyer, B. A. & Johnston, R. E. (1984) Science 225, 424-427 and Olmsted, R. A., Meyer, W. J. & Johnston, R. E. (1986) Virology 148, 1-10). The nucleotide sequence data suggest that a single mutation in the E2 gene is sufficient to cause these coordinate phenotypic changes. These findings identify a single locus in a Sindbis virus surface glycoprotein gene that determines both efficiency of interaction with cultured baby hamster kidney cells and degree of virulence in neonatal mice.
authors.forename: N L
authors.initials: NL
authors.lastname: Davis
authors.forename: F J
authors.initials: FJ
authors.lastname: Fuller
authors.forename: W G
authors.initials: WG
authors.lastname: Dougherty
authors.forename: R A
authors.initials: RA
authors.lastname: Olmsted
authors.forename: R E
authors.initials: RE
authors.lastname: Johnston
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002478:Cells, Cultured; D005814:Genes, Viral; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D051379:Mice; D009154:Mutation; D012845:Sindbis Virus / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D006023:Glycoproteins