Type I interferon alpha subtype inhibition of la crosse virus infection in muscles cells and neurons 4575

Abstract Description La Crosse Encephalitis virus (LACV) is the leading cause of pediatric mosquito-borne encephalitis in North America. Infection is established in the layer of skin-associated muscle following a mosquito blood meal, but the virus ultimately reaches the brain and causes neuronal cell death. In the current study, we analyzed the innate immune response in the two primary cell types infected by LACV, muscle cells in the skin and neurons in the brain. We utilized human cell lines of muscle (M007) and neuronal (SH-SY5Y) origin to assess the antiviral responses to virus infection with type I interferon (IFN) treatment. LACV replicates inefficiently in the M007 cells, which are resistant to LACV-mediated death. In contrast, the SH-SY5Y cells succumb to infection after two days with high virus titers. We found differences between the cell types in the ability of the type I IFNs to protect against virus infection and in interferon stimulated gene (ISG) expression. We also saw differences between the type I IFN subtypes in their ability to protect both M007 and SH-SY5Y cells against LACV infection. These experiments identify cell-type specific responses to LACV infection which help to define mechanisms of LACV pathogenesis. Funding Sources National Institute of Allergy and Infectious Diseases, National Institutes of Health Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)