SEQUENCE-ANALYSIS OF THE AVIRULENT, DEMYELINATING A7 STRAIN OF SEMLIKI-FOREST-VIRUS

The nonstructural region of the genome of the avirulent A7 strain of S emliki Forest virus (SFV) has been sequenced, so that the complete nuc leotide sequence is available. Compared to the virulent SFV4 strain (p roduced from the infectious clone pSF6-SFV4), A7 contains 226 nucleoti de changes in the translated region, which result in 47 amino acid cha nges. The 5' nontranslated region has two nucleotide changes, and the 3' nontranslated region is longer in A7 than SFV4, and contains diverg ent and repeated sequences. Chimeras containing SFV4 and A7 sequences and an infectious clone of A7, pSP6-CA7, were constructed. The virulen ce of these was tested by intraperitoneal and intranasal infection of adult BALB/c mice. It was shown that determination of the avirulent ph enotype of A7 was polygenic, and required the additive effect of seque nces from both the structural and nonstructural regions of the SFV gen ome.