VARIABILITY OF HERPES-SIMPLEX VIRUS-1 GL AND ANTI-GL ANTIBODIES THAT INHIBIT CELL-FUSION BUT NOT VIRAL INFECTIVITY

Herpes simplex virus type 1 gL lacks a transmembrane domain but stably associates with membranes through its oligomerization with the integr al membrane glycoprotein designated gH. The gH-gL oligomers are essent ial for virion infectivity and virus-induced cell fusion. Monoclonal a nd polyclonal antibodies were raised against HSV-1(KOS) gL as probes f or antigenic structure and functional protein domains. Antigenic deter minants recognized by these antibodies were found to be present on gL expressed by many, but not all, strains of HSV-1 and were not detected on gL expressed by HSV-2 strains. These antigenic determinants were l ocalized to the C-terminal region of HSV-1 gL, where amino acid substi tutions define at least two classes of HSV-1 gL and where the sequence s of HSV-1 and HSV-2 gL diverge considerably. The antibodies were extr emely effective at inhibiting virus-induced cell fusion, provided the virus strain expressed the relevant antigenic determinants, but failed to neutralize viral infectivity despite demonstrable binding to virio ns. These results define strain-dependent differences in the structure and antigenic conformation of HSV-1 forms of gL and suggest that the roles of gL in cell fusion and viral entry are different. (C) 1996 Aca demic Press, Inc.