Malaria abrogates O’nyong–nyong virus pathologies by restricting virus infection in nonimmune cells

Abstract

O’nyongnyong virus (ONNV) is a re-emerging alphavirus previously known to be transmitted by main malaria vectors, thus suggesting the possibility of coinfections with arboviruses in co-endemic areas. However, the pathological outcomes of such infections remain unknown. Using murine coinfection models, we demonstrated that a preexisting blood-stagePlasmodiuminfection suppresses ONNV-induced pathologies. We further showed that suppression of viremia and virus dissemination are dependent onPlasmodium-induced IFNγ and are associated with reduced infection of CD45−cells at the site of virus inoculation. We further proved that treatment with IFNγ or plasma samples fromPlasmodium vivax–infected patients containing IFNγ are able to restrict ONNV infection in human fibroblast, synoviocyte, skeletal muscle, and endothelial cell lines. Mechanistically, the role of IFNγ in restricting ONNV infection was confirmed in in vitro infection assays through the generation of an IFNγ receptor 1 α chain (IFNγR1)–deficient cell line.