Selective decoupling of IgG1 binding to viral Fc receptors restores antibody-mediated NK cell activation against HCMV.

ABSTRACT: Antibodies binding cell-surface antigens to activate cellular immunity are an important mechanism of anti-viral protection, yet antibodies targeting cells infected by human cytomegalovirus (HCMV) exhibit limited efficacy. This is due to HCMV immune evasion mechanisms, including viral receptors (vFcγRs) that bind human immunoglobulin G Fc domains to inhibit host Fcγ receptor activation and impair Fc-mediated immune functions. Here, we biochemically characterize two conserved vFcγRs, gp34 and gp68, and map their Fc binding sites. We then engineer Fc variants to retain binding to host Fc receptors CD16A and FcRn but exhibit markedly reduced gp34/gp68 interactions. Antibodies targeting the gB fusogen with engineered Fc domains are not internalized by infected cells, mediate enhanced immune cel

SUBMITTER: Qerqez AN 

PROVIDER: S-EPMC12831531 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature