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-stage Plasmodium infection suppresses ONNV-induced pathologies. We further showed that suppression of viremia and virus dissemination are dependent on Plasmodium-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 from Plasmodium 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.
Highlights
O’nyongnyong virus (ONNV) is an enveloped, positive-sense, singlestranded RNA virus that belongs to the Alphavirus genus of the Togaviridae family [1]
3-wk-old C57BL/6J mice were inoculated with 1E6-infected red blood cells from either Plasmodium berghei ANKA clone 231cl1 (PbA), which induces lethal neuropathology known as experimental cerebral malaria (ECM), or the nonlethal self-resolving strain Plasmodium yoelii 17XNL clone 1.1 (Py17x)
O’nyongnyong virus and Plasmodium parasites share common anopheline vectors and co-circulate in sub-Saharan Africa with risk of human coinfection. This is the first study investigating the pathological outcomes of coinfection by Plasmodium parasites and alphavirus ONNV in a mammalian host
Summary
O’nyongnyong virus (ONNV) is an enveloped, positive-sense, singlestranded RNA virus that belongs to the Alphavirus genus of the Togaviridae family [1]. ONNV was first isolated in 1959 in Gulu, Uganda [4], during an outbreak that lasted 3 yr (1959–1962) and involved more than two million cases [5]. Epidemiological surveys have reported high seroprevalence of ONNV in Coastal Kenya [8] and Uganda [9], suggesting an underestimated burden of ONNV infections in sub-Saharan Africa. 6. Rwaguma EB, Lutwama JJ, Sempala SD, Kiwanuka N, Kamugisha J, Okware S, Bagambisa G, Lanciotti R, Roehrig JT, Gubler DJ (1997) Emergence of epidemic O’nyong-nyong fever in southwestern Uganda, after an absence of 35 years. 8. LaBeaud AD, Banda T, Brichard J, Muchiri EM, Mungai PL, Mutuku FM, Borland E, Gildengorin G, Pfeil S, Teng CY, et al (2015) High rates of O’nyong nyong and Chikungunya virus transmission in coastal Kenya. PLoS Negl Trop Dis 9: e0003436. doi:10.1371/journal.pntd.0003436
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