ANTIGENIC STRUCTURE OF SOLUBLE HERPES-SIMPLEX VIRUS (HSV) GLYCOPROTEIN-D CORRELATES WITH INHIBITION OF HSV INFECTION

Soluble forms of herpes simplex virus (HSV) glycoprotein D (gD) block viral penetration. Likewise, most HSV strains are sensitive to gD-medi ated interference by cells expressing gD. The mechanism of both forms of gD-mediated inhibition is thought to be at the receptor level. We a nalyzed the ability of different forms of soluble, truncated gD (gDt) to inhibit infection by different strains of HSV-1 and HSV-2. Strains that were resistant to gD-mediated interference was also resistant to inhibition by gDt, thereby suggesting a link between these two phenome na. Virion gD was the major viral determinant for resistance to inhibi tion by gDt. An insertion-deletion mutant, gD-1(Delta 290-299t), had a n enhanced inhibitory activity against most strains tested. The struct ure and function of gDt proteins derived from the inhibition-resistant viruses rid1 adn ANG were analyzed. gD-1(rid1t) and gD-1(ANGt) had a potent inhibitory effect on plaque formation by wild-type strains of H SV but, surprisingly, little or not effect on their parental strains. As measured by quantitive enzyme-linked immunosorbent assay with a div erse panel of monoclonal antibodies, the antigenic structures of gD-1( rid1t) and gD-1(ANGt) were divergent from that of the wild type yet we re similar to each other and to that of gD-1(Delta 290-299t). Thus, th ree different forms of gD have common antigenic changes correlate with enhanced inhibitory activity against HSV. We conclude that inhibition of HSV infectivity by soluble gD is influenced by the antigenic confo rmation of the blocking gDt as well as the form of gD in the target vi rus.