ADAPTABILITY IN HERPESVIRUSES - GLYCOPROTEIN D-INDEPENDENT INFECTIVITY OF PSEUDORABIES VIRUS

Initial contact between herpesviruses and host cells is mediated by vi rion envelope glycoproteins which bind to cellular receptors, In sever al alphaherpesviruses, the nonessential glycoprotein gC has been found to interact with cell surface proteoglycans, whereas the essential gl ycoprotein gD is involved in stable secondary attachment, In addition, gD is necessary for penetration, which involves fusion between virion envelope and cellular cytoplasmic membrane, As opposed to other alpha herpesvirus gD homologs, pseudorabies virus (PrV) gD is not required f or direct viral cell-to-cell spread, Therefore, gD(-) PrV can be passa ged in noncomplementing cells by cocultivating infected and noninfecte d cells, Whereas infectivity was found to be strictly cell associated in early passages, repeated passaging resulted in the appearance of in fectivity in the supernatant, finally reaching titers as high as 10(7) PFU/ml (PrV gD(-) Pass), Filtration experiments indicated that this i nfectivity was not due to the presence of infected cells, and the abse nce of gD was verified by Southern and Western blotting and by virus n eutralization. Infection of bovine kidney cells constitutively express ing PrV gD interfered with the infectivity of wild type PrV but did no t inhibit that of PrV gD(-) Pass, Similar results were obtained after passaging of a second PrV mutant, PrV-376, which in addition to gD als o lacks gG, gI, and gE, Penetration assays demonstrated that PrV gD(-) Pass entered cells much more slowly than wild-type PrV. In summary, o ur data demonstrate the existence of a gD-independent mode of initiati on of infection in PrV and indicate that the essential function(s) tha t gD performs in wild-type PrV infection can be compensated for after passaging. Therefore, regarding the requirement for gD, PrV seems to b e intermediate between herpes simplex virus type I, in which gD is nec essary for penetration and cell-to-cell spread, and varicella-zoster v irus (VZV), which lacks a gD gene, Our data show that the relevance of an essential protein can change under selective pressure and thus dem onstrate a way in which VZV could have evolved from a PrV-like ancesto r.