Cellular expression of bovine herpesvirus 1 gD inhibits cell-to-cell spread of two closely related viruses without blocking their primary infection.

Alphaherpesviral glycoprotein D (gD) is a critical component of the cell membrane penetration system. Cells that express gD of herpes simplex virus type 1 (HSV1), pseudorabies virus (PRV), or bovine herpesvirus type 1.1 (BHV1.1) resist infection by the homologous virus due to interference with viral entry at the level of penetration. BHV1.1 gD interferes with the distantly related viruses HSV1 and PRV despite only a 30-40% sequence similarity and the complete absence of antigenic cross-reactivity among the three gDs. The six cysteines that form three intrachain disulfide bonds in HSV1 are also present in PRV and BHV1.1 gD, suggesting structural similarities among the gD homologs. Functional similarities were postulated to be responsible for cross-interference. To test this hypothesis, we constructed a BHV1.1 gD-expressing cell line (MDBKgD) and assessed its resistance to the homologous BHV1.1 and two closely related viruses, BHV1.2 and BHV5. The gDs of these viruses share 98. 3% and 86% amino acid identity with BHV1.1 gD and bound monoclonal antibodies directed against all five neutralizing epitopes mapped on BHV1.1 gD. MDBKgD cells were resistant to BHV1.1 but fully susceptible to BHV1.2 and BHV5 infection as measured by plaque numbers and single cycle growth kinetics. However, all three viruses, but not vesicular stomatitis virus, made smaller plaques on MDBKgD cells than on control cells. These data suggest that gD-mediated interference is expressed both at the level of initial infection and at the level of cell-to-cell spread and that these two levels can be distinguished by using closely related viruses. Copyright 1999 Academic Press.