Role of anti-gB and -gD antibodies in antibody-induced endocytosis of viral and cellular cell surface glycoproteins expressed on pseudorabies virus-infected monocytes

The addition of porcine pseudorabies virus (PN)-specific polyclonal IgG ant ibodies to PrV-infected monocytes induces internalization of plasma membran e-anchored viral glycoproteins and major histocompatibility complex (MHC) c lass I. Using PrV deletion strains, it was shown that gB and go are essenti al for the process to occur. The purpose of the current study was to evalua te whether antibodies directed against single viral glycoproteins are able to induce endocytosis. It was shown that monoclonal antibodies directed aga inst viral glycoprotein gB and go, but not against gC and gE, are able to i nduce internalization of their respective ligand. Adding a combination of m onoclonal antibodies against gB and go resulted in endocytosis levels, comp arable to the endocytosis levels observed when adding porcine PrV-specific polyclonal antibodies. The addition of genistein and tyrphostin 25, two inh ibitors of tyrosine kinase activity, abolished endocytosis induced by monoc lonal anti-gB and -gD antibodies in a concentration-dependent manner. The a ddition of similar concentrations of tyrphostin 1, an inactive tyrphostin, had no effect on endocytosis. It was also shown that a mixture of polyclona l, but not monoclonal, antibodies against gB and go is able to induce coint ernalization of MHC class I. This indicates that MHC class I cointernalizat ion results from a passive catching of the molecules rather than from a spe cific interaction of the MHC class I molecules with one or more viral glyco proteins. In conclusion, it can be stated that antibody-induced crosslinkin g of gB and go induces the activation of a tyrosine phosphorylation-depende nt signal transduction pathway, leading to their endocytosis. Cointernaliza tion of other viral glycoproteins and MHC class I is most likely caused by a passive catching of these molecules in the gB and go aggregates. (C) 2000 Academic Press.