GLYCOPROTEIN-B IS A SPECIFIC DETERMINANT OF HERPES-SIMPLEX VIRUS TYPE-1 NEUROINVASIVENESS

Herpes simplex virus type 1 strains ANG and KOS lack neuroinvasiveness when inoculated on the footpads of mice, and because the strains are able to complement each other, the genes associated with this phenotyp e differ. In this study, we used marker rescue techniques to show that at least two genes cloned from ANG are required to restore neuroinvas iveness to KOS. One of the two fragments required is the 6.3-kb BamHI- A/EcoRI-D fragment (0.15 to 0.19 map units). The second has been ident ified as the sequence encoding glycoprotein B (gB) (UL27). Analysis of ANG and KOS DNA sequences in the relevant region of the gB gene revea led two nucleotide differences which result in amino acid differences in the gB protein. One appears to be unique to the strain of KOS used in our laboratory. The second, at codon 523 of the mature gB protein, encodes a valine in KOS and an alanine in ANG. Recombinant KOS viruses which contained ANG sequences in this region were constructed, and tw o independently selected recombinants demonstrated increased neuroinva siveness in mice. From these results, we conclude that gB significantl y influences neuroinvasiveness. Mechanisms by which this might occur a re discussed.