CYCLOSPORINE-A RESISTANCE OF HERPES-SIMPLEX VIRUS-INDUCED FUSION FROMWITHIN AS A PHENOTYPICAL MARKER OF MUTATIONS IN THE SYN-3 LOCUS OF THE GLYCOPROTEIN-B GENE

We here report research in which nine strains of Herpes simplex virus (HSV) with fusing activity were investigated in order to establish pre cise phenotypical markers of mutations in the carboxy terminus of glyc oprotein B (gB). The gene region encoding the carboxy terminus of gB w as isolated, then cloned, and finally sequenced. Our investigation sho wed that seven strains have different mutations in the syn 3 locus. We observed no base difference in the gB gene region encoding the carbox y terminus of gB of two other strains. Strains with a mutation in the carboxy terminus of gB induced fusion from within (FFWI) in the presen ce of Cyclosporin A (CyA) at a concentration up to 150 mu M. There are two clusters of mutations correlated with the syn 3 locus and selecte d in the presence of CyA: One group comprised of amino acid substituti ons at position 816, the other of changes at positions 853, 854, and 8 57. In contrast, the fusion induced by strains with mutations in other syn loci is CyA sensitive. CyA inhibits the FFWI at concentrations of 20-60 mu M. The results demonstrate the CyA resistance of HSV-induced FFWI should serve as a phenotypical marker of mutations in the carbox y terminus of gB. Moreover, our investigations revealed that fusion fr om without (FFWO) does not always serve as a phenotypical marker of mu tations in the syn 3 locus. On the one hand, all FFWO-positive strains possess a syn 3 locus mutation, whilst, on the other hand, five strai ns with mutations in the carboxy terminus of gB are FFWO negative. Lac k of FFWO of some strains might originate from genetic determinants ou tside of the syn 3 locus of the gB gene.