Dunagan Megan M, Dábilla Nathânia, McNinch Colton, Brenchley Jason M, Dolan Patrick T, Fox Julie M
Emerging Virus Immunity Unit, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Quantitative Virology and Evolution Unit, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
bioRxiv. 2024 Jul 24:2024.07.23.604823. doi: 10.1101/2024.07.23.604823.
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.
马亚罗病毒（MAYV）是一种新出现的虫媒病毒。先前的研究表明，抗体Fc效应器功能对于单克隆抗体介导的针对甲病毒的最佳保护至关重要；然而，在自然感染期间，Fcγ受体（FcγRs）对保护的需求尚未得到评估。在此，我们发现缺乏激活型FcγRs（FcRγ）的小鼠出现了病程延长的临床疾病，关节相关组织中的病毒更多。病毒清除与抗MAYV细胞表面结合而非中和抗体相关。缺乏Fc-FcγR相互作用会在慢性时间点增加单核细胞数量。单细胞RNA测序显示，关节相关组织中促炎性单核细胞水平升高，FcRγ单核细胞和巨噬细胞中存在的MAYV RNA增加。将FcRγ单核细胞转移到野生型动物中足以增加关节相关组织中的病毒。总体而言，这项研究表明，抗体Fc与激活型FcγRs的相互作用在MAYV感染期间促进了保护性反应，并防止单核细胞成为潜在的感染靶点。
