Activating FcγRs on monocytes are necessary for optimal Mayaro virus clearance.

Mayaro virus (MAYV) is an emerging arbovirus. Previous studies have shown antibody Fc effector functions are critical for optimal monoclonal antibody-mediated protection against alphaviruses; however, the requirement of Fc gamma receptors (FcγRs) for protection during natural infection has not been evaluated. Here, we showed mice lacking activating FcγRs (FcRγ) developed prolonged clinical disease with more virus in joint-associated tissues. Viral clearance was associated with anti-MAYV cell surface binding rather than neutralizing antibodies. Lack of Fc-FcγR engagement increased the number of monocytes through chronic timepoints. Single cell RNA sequencing showed elevated levels of pro-inflammatory monocytes in joint-associated tissue with increased MAYV RNA present in FcRγ monocytes and macrophages. Transfer of FcRγ monocytes into wild type animals was sufficient to increase virus in joint-associated tissue. Overall, this study suggests that engagement of antibody Fc with activating FcγRs promotes protective responses during MAYV infection and prevents monocytes from being potential targets of infection.