A heterologous heparin-binding domain can promote functional attachment of a pseudorabies virus gC mutant to cell surfaces.

The efficient attachment of pseudorabies virus to cultured cells is dependent on an electrostatic interaction between negatively charged cell surface heparan sulfate and the viral envelope glycoprotein gC. Deletion of the first one-third of gC severely impairs virus attachment, but the mutant virions are still capable of entering cells and establishing an infection via a gC-independent pathway. This region of gC contains three clusters of positively charged amino acids that exactly or nearly conform to proposed consensus motifs for heparin-binding domains (HBDs), and the loss of one or more of these potential HBDs may be responsible for the observed attachment defect. To more directly show the involvement of HBDs in pseudorabies virus attachment to cells, we replaced the first one-third of gC with a single, biochemically defined HBD from apolipoprotein B-100. On the basis of the results of attachment, penetration, and heparin competition assays, the heterologous HBD mediated heparan sulfate-dependent virus attachment, but not to fully wild-type levels. Although the intermediate phenotype is not understood, the apolipoprotein B-100 HBD may represent the smallest defined amino acid sequence that promotes functional herpesvirus attachment to cultured cells.