Bovine herpesvirus 1-induced apoptotic cell death: Role of glycoprotein D

Bovine herpesvirus 1 (BHV-1) induces apoptotic cell death in peripheral blo od mononuclear cells and in bovine B lymphoma (BL-3) cells. Attachment but not penetration of BHV-1 is necessary to induce apoptosis in target cells, suggesting that one or more BHV-1 envelope glycoproteins could be involved in the activation of the apoptotic process. In the present study, we demons trate that, although BHV-1 Virions devoid of glycoprotein D (BHV-1 gD-/-) s till bind to BL-3 cells, they are no longer able to induce apoptosis. In co ntrast, virions that contain glycoprotein D (gD) in the viral envelope but do not genetically encode gD (BHV-1 gD-/+) induce a level of apoptosis comp arable to that produced by wild-type (wt) BHV-1. In addition, monoclonal an tibodies directed against gD, but not against gB or gC, strongly reduced th e high levels of apoptosis induced by BHV-1. These observations demonstrate that the induction of apoptosis is directly due to BHV-1 viral particles h arboring gD in the viral envelope. Interestingly, binding of affinity-purif ied gD to BL-3 cells did not induce apoptosis but inhibited the ability of wt BHV-1 to induce apoptosis. Altogether, these results provide evidence fo r the direct or indirect involvement of gD in the mechanism by which BHV-1 induces apoptosis. (C) 1999 Academic Press.