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Interaction of the endogenous antibody response with activating FcgRs enhance control of Mayaro virus through monocytes

ABSTRACT: 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 (FcgRs) for protection during natural infection has not been evaluated. Here, we showed mice lacking activating FcgRs (FcRg-/-) developed prolonged clinical disease with more MAYV in joint-associated tissues. Viral clearance was associated with anti-MAYV cell surface binding antibodies rather than neutralizing antibodies. Lack of Fc-FcgR 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 FcRg-/- monocytes and macrophages. Transfer of FcRg-/- 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 FcgRs promotes protective responses during MAYV infection and prevents a pro-viral role for monocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE285678 | GEO | 2025/02/05

REPOSITORIES: GEO

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Interaction of the endogenous antibody response with activating FcgRs enhance control of Mayaro virus through monocytes

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