Neutralizing antibodies detect a disulfide-linked glycoprotein complex within the envelope of human cytomegalovirus.

The specificity of neutralizing antibodies for human cytomegalovirus (CMV) envelope proteins was studied by comparing the reactivity of human CMV immune sera with that of a group of CMV-specific monoclonal antibodies. Characterization of this group of monoclonal antibodies revealed that six antibodies bound intact virions, and four of these antibodies neutralized infectious virus in vitro. All of the monoclonal antibodies, as well as human immune sera, precipitated three virion glycoproteins of estimated molecular weights of 160-K 116K, and 55K. Human immune sera also precipitated proteins of estimated molecular weights of 200K, 145K, 100K, 66K, and 34K. The three envelope glycoproteins detected by both the neutralizing monoclonal antibodies and immune human sera were shown to exist as a covalently linked, disulfide-bonded protein complex within virions. This result provided an explanation for the reactivity with multiple proteins of such highly specific reagents as monoclonal antibodies. Furthermore, these findings suggested that determinant(s) detected by CMV-neutralizing antibodies were expressed by this complex of envelope proteins.