Suppression of Fcγ-Receptor-Mediated Antibody Effector Function during Persistent Viral Infection

Understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. T cell exhaustion during chronic viral infection is well described, but effects on anti-body- mediated effector activity are unclear. Herein, we show that increased amounts of immune complexes generated in mice persistently infected with lymphocytic choriomeningitis virus (LCMV) suppressed multiple Fc gamma-receptor (Fc gamma R) functions. The high amounts of immune complexes suppressed antibody-mediated cell depletion, therapeutic antibody- killing of LCMV infected cells and human CD20-expressing tumors, as well as reduced immune complex-mediated cross-presentation to T cells. Suppression of Fc gamma R activity was not due to inhibitory Fc gamma Rs or high concentrations of free antibody, and proper Fc gamma R functions were restored when persistently infected mice specifically lacked immune complexes. Thus, we identify a mechanism of immunosuppression during viral persistence with implications for understanding effective antibody activity aimed at pathogen control.