SYNCYTIAL MUTATIONS IN THE HERPES-SIMPLEX VIRUS TYPE-1 GK-(UL53) GENEOCCUR IN 2 DISTINCT DOMAINS

Syncytial (syn) mutants of herpes simplex virus cause cell fusion. Man y syn mutations map to the syn1 locus, which has been identified with the gK (UL53) gene. In this work, the gK; genes of eight syn mutants d erived from the KOS strain were sequenced to identify residues and, po ssibly, domains important for the fusion activity of mutant gK. DNA se quencing showed that six mutants (syn30, syn31, syn32, syn102, syn103, and syn105) had single missense mutations in the gK gene. Two of thes e, syn31 and syn32, had identical mutations that caused the introducti on of a potential site for N-linked glycosylation. syn31 gK was analyz ed by in vitro translation and found to utilize the novel glycosylatio n site. Two other mutants, syn8 and syn33, had three mutations each, r esulting in three amino acid substitutions in syn8 and two substitutio ns in syn33. Of the 10 gK syn mutant sequences known, 8 have mutations in the N-terminal domain of gK, suggesting that this domain, which is likely to be an ectodomain, is important for the function of the prot ein. The other two mutants, syn30 and syn103, have mutations near the C terminus of gK.