The critical role of interleukin-6 in protection against neurotropic flavivirus infection

• DOI: 10.3389/fcimb.2023.1275823
• Publication Date: 2023-11-16T17:33:32Z
• Authors: Tabassum T. Auroni; Komal Arora; Janhavi P. Natekar; Heather Pathak; Amany Elsharkawy; Mukesh Kumar
• Keywords: Flavivirus; Viremia; Viral encephalitis

West Nile virus (WNV) and Japanese encephalitis (JEV) are emerging mosquito-borne flaviviruses causing globally. No specific drug or therapy exists to treat flavivirus-induced neurological diseases. The lack of therapeutics underscores an urgent need determine the function important host factors involved in flavivirus replication disease progression. Interleukin-6 (IL-6) upregulation has been observed during viral infections both mice humans, implying that it may influence outcome significantly. Herein, we investigated IL-6 pathogenesis neurotropic infections. First, examined role flavivirus-infected human neuroblastoma cells, SK-N-SH, found neutralization increased WNV JEV inhibited expression key cytokines. We further evaluated by infecting primary mouse cells derived from knockout (IL-6 −/− ) wild-type (WT) with JEV. results exhibited yields lacking gene. Next, our vivo approach revealed had significantly higher morbidity mortality after subcutaneous infection pathogenic NY99 Nakayama strain compared WT mice. non-pathogenic Eg101 did not cause but resulted 60% mice, indicating is required for survival peripheral inoculation also viremia brain load than Subsequently, explored innate immune responses infection. Our data demonstrated reduced levels cytokines serum early elevated proinflammatory later, along suppressed anti-inflammatory In addition, mRNA IFN-α IFN-β was lower infected conclusion, these suggest exacerbates vitro increase dysregulating response.