STING is required for host defense against neuropathological West Nile virus infection

• DOI: 10.1371/journal.ppat.1007899
• Publication Date: 2019-08-15T17:30:12Z
• Authors: Kathryn McGuckin ...; Piper M. Treuting; Emily A. Hemann; Katharina Esser-N...; Annelise G. Snyder; Jessica B. Graham; Brian P. Daniels; Courtney Wilkins; Jessica M. Snyder; Kathleen M. Voss; Andrew Oberst; Jennifer Lund; Michael Gale
• Keywords: Sting; Flavivirus

West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity mortality in United States. WNV infections are acutely controlled by innate immunity peripheral tissues outside central nervous system (CNS) but can evade actions interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, death. Recent studies indicate that STimulator INterferon Gene (STING), canonically known for initiating a type I IFN production immune response cytosolic DNA, required host defense against neurotropic viruses. We evaluated role STING control infection pathology murine model infection. When challenged with WNV, knock out (-/-) mice displayed increased compared wild (WT) mice. Virologic analysis assessment activation revealed signaling was not spleen nor sufficient mediate canonical vitro. However, STING-/- exhibited clear trend viral load virus dissemination CNS. found prolonged neurological signs WT Pathological examination lesions, mononuclear cellular infiltration neuronal death mice, sustained after clearance. bone marrow derived macrophages early replication activation. In vivo, developed aberrant T cell both brain during linked Our findings demonstrate plays critical programming disease.