IFN-β contributes to astrocyte activation in the brain following coronavirus PHEV infection independent on peripheral immunity

Porcine hemagglutinating encephalomyelitis (PHE), caused by a betacoronavirus named porcine hemagglutinating encephalomyelitis virus (PHEV), is a highly fatal disease of pigs characterized by nonsuppurative encephalitis. Activation of astrocytes is a hallmark of viral encephalomyelitis; however, the mechanism of PHEV-induced astrocyte activation is currently unknown. Based on mouse model, we show that PHEV infection led to astrogliosis in mouse brain and brain slice cultures (BSCs), as indicated by increased expression of glial fibrillary acidic protein (GFAP). PHEV can neither infect nor activate primary astrocytes in vitro, indicating that activation of astrocytes maybe mediated by factors secreted from viral infected neurons but not by direct viral infection of astrocytes. PHEV infection results in increased interferon (IFN) response in later stage, we thereafter focused on whether IFN-β can activate astrocytes after PHEV infection similar to other neurotropic viruses. IFN-β treatment resulted in both the upregulation of GFAP and activation-associated cytokines/chemokines in mouse primary astrocytes. Furthermore, the addition of IFN-β neutralization antibody prevented PHEV-infected mouse brain tissue homogenate from activating astrocytes. Taken together, IFN-β triggers the activation of astrocytes in the central nervous system (CNS) following PHEV infection. Further understanding of the role of activated astrocytes during PHEV infection may provide new insights for treatment this disease.