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dc.contributor.authorHerrero, Laraen_US
dc.contributor.authorNelson, Michelleen_US
dc.contributor.authorSrikiatkhachorn, Anonen_US
dc.contributor.authorGu, Ranen_US
dc.contributor.authorAnantapreecha, Surapeeen_US
dc.contributor.authorFingerle-Rowson, Günteren_US
dc.contributor.authorBucala, Richarden_US
dc.contributor.authorMorand, Ericen_US
dc.contributor.authorSantos, Leilani L.en_US
dc.contributor.authorMahalingam, Sureshen_US
dc.description.abstractArthrogenic alphaviruses, such as Ross River virus (RRV), chikungunya, Sindbis, mayaro and o'nyong-nyong viruses circulate endemically worldwide, frequently causing outbreaks of polyarthritis. The exact mechanisms of how alphaviruses induce polyarthritis remain ill defined, although macrophages are known to play a key role. Macrophage migration inhibitory factor (MIF) is an important cytokine involved in rheumatoid arthritis pathogenesis. Here, we characterize the role of MIF in alphavirus-induced arthritides using a mouse model of RRV-induced arthritis, which has many characteristics of RRV disease in humans. RRV-infected WT mice developed severe disease associated with up-regulated MIF expression in serum and tissues, which corresponded to severe inflammation and tissue damage. MIF-deficient (MIF-/-) mice developed mild disease accompanied by a reduction in inflammatory infiltrates and muscle destruction in the tissues, despite having viral titers similar to WT mice. In addition, reconstitution of MIF into MIF-/- mice exacerbated RRV disease and treatment of mice with MIF antagonist ameliorated disease in WT mice. Collectively, these findings suggest that MIF plays a critical role in determining the clinical severity of alphavirus-induced musculoskeletal disease and may provide a target for the development of antiviral pharmaceuticals. The prospect being that early treatment with MIF-blocking pharmaceuticals may curtail the debilitating arthritis associated with alphaviral infections.en_US
dc.publisherNational Academy of Sciencesen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalProceedings of the National Academy of Sciences of USAen_US
dc.subject.fieldofresearchHumoural Immunology and Immunochemistryen_US
dc.titleCritical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositisen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomicsen_US
gro.hasfulltextNo Full Text

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