Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity

Abstract

Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFc{gamma}Rs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine the in vivo function of vFc{gamma}Rs in animal hosts closely related to humans, we identified and characterized vFc{gamma}Rs encoded by rhesus CMV (RhCMV). We demonstrate that Rh05, Rh152/151 and Rh173 represent the complete set of RhCMV vFc{gamma}Rs, each displaying functional similarities to their respective HCMV orthologs with respect to antagonizing host Fc{gamma}R activation in vitro. When RhCMV-naive rhesus macaques were infected with vFc{gamma}R-deleted RhCMV, peak plasma viremia levels and anti-RhCMV antibody responses were comparable to wildtype infections. However, the duration of plasma viremia was significantly shortened in immunocompetent, but not in CD4+ T cell-depleted animals. Since vFc{gamma}Rs were not required for superinfection, we conclude that vFc{gamma}Rs delay control by virus-specific adaptive immune responses, particularly antibodies, during primary infection.