Immune responses in Mayaro infected mice and its relation with viral replication and muscle damage

Abstract

Mayaro virus (MAYV) is a tropical arbovirus first described in forest regions of the South America, and recently associated with urban circulation. Mayaro infections leads to a disease with high rate of persistent arthralgia and myalgia in humans. Despite this, pathogenesis and host immune response of MAYV infections are still limited. The aim of this work was to evaluate the immune response and cell profile during MAYV infections. We developed a disease model infecting SV129 wild-type (WT), SVA129 Type I Interferon receptor deficient (IFNAR−/−), C57BL/6 WT and C57BL/6 recombination activation gene-1 deficient (RAG−/−) mice, and accessing replication, tissue damage, and inflammation through time. While adult WT mice are resistant to infection, IFNAR−/− mice exhibited increasing viral load up to 6 days after infection, footpad swelling, lethargy and weight loss. Histological analysis showed extensive necrosis sites in infected IFNAR−/− mice and also presence of mononucleated cell infiltrate. We detected elevated expression of inflammatory cytokines like TNF, IL-6, KC, IL-1, MCP-1 and RANTES, and decreased TGF-beta in infected muscle. In RAG−/− mice, MAYV infection lead to a persistent replication being detected at blood and tissues up 40 days post infection. However, infected RAG−/− mice did not develop any signs of muscle damage or infiltrate during early and late infection and neither the expression inflammatory cytokines. So far, our data demonstrates that innate and adaptive immunity are critical to restrict MAYV replication. Adaptive immunity is also involved in MAYV-induced tissue damage. These results contribute in underlying MAYV pathogenesis and further experiments must to be made to elucidate the mechanisms involved.