DNA Extracellular Traps Released by Mayaro Virus-Infected Macrophages Act as a Platform for Virus Dissemination

Mayaro virus (MAYV) is an arthritogenic arbovirus that causes a debilitating illness that can progress to a chronic rheumatic disease characterized by persistent viral replication in macrophages within joint tissues. Here, we report that MAYV-infected macrophages release decondensed DNA traps (DNA extracellular traps, DETs) through a mechanism driven by the production of reactive oxygen species and peptidyl arginine deiminase activation, resembling the classical mechanism of pathogen clearance by activated neutrophils. Unlike traditional pathogen clearance observed for NETs released by neutrophils, MAYV-induced DETs did not inactivate the virus. Instead, DET-ensnared viruses are internalized by neighboring uninfected macrophages, increasing the number of infected cells. Collectively, these findings suggest that MAYV-containing DETs act as a “Trojan horse” that facilitates viral dissemination within inflamed tissues, connecting macrophage-mediated inflammatory response to viral persistence in the articular tissue in chronic MAYV disease.