Human cytomegalovirus gH/gL/gO binding to PDGFRα provides a regulatory signal activating the fusion protein gB that can be blocked by neutralizing antibodies

Development of vaccines and therapeutics targeting the fusion apparatus of human cytomegalovirus (HCMV) has been limited by the lack of an <i>in vitro</i> cell-cell fusion assay that faithfully models the receptor-dependent fusion characteristic of HCMV entry. The cell-cell fusion assay described here demonstrated that the binding of gH/gL/gO to its receptor, PDGFRα, serves to regulate the activity of the fusion protein gB, and this is specifically vulnerable to inhibition by neutralizing antibodies. Moreover, the measurement of fusion kinetics allows for mutational studies of the fusion mechanism, assessing the influence of genetic diversity among the viral glycoproteins and studying the mechanism of neutralizing antibodies.