Porcine Hemagglutinating Encephalomyelitis Virus Activation of the Integrin α5β1-FAK-Cofilin Pathway Causes Cytoskeletal Rearrangement To Promote Its Invasion of N2a Cells.

摘要: Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic that causes diffuse neuronal infection with neurological damage and high mortality. Virus-induced cytoskeletal dynamics are thought to be closely related this type of nerve damage. Currently, the regulation pattern actin cytoskeleton its molecular mechanism remain unclear when PHEV enters host cells. Here, we demonstrate entry into N2a cells induces biphasic remodeling dynamic change in cofilin activity. Viral affected by disruption kinetics or alteration binds integrin α5β1 then initiates α5β1-FAK signaling pathway, leading virus-induced early phosphorylation F-actin polymerization. Additionally, Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division cycle 42 (Cdc42), downstream regulatory gene p21-activated protein kinases (PAKs) recruited as mediators PHEV-induced changes activity pathway. In conclusion, utilizes α5β1-FAK-Rac1/Cdc42-PAK-LIMK-cofilin pathway cause an rearrangement promote own invasion, providing theoretical support for development pathogenic mechanisms new antiviral targets.IMPORTANCE PHEV, member Coronaviridae family, typical primarily affects nervous system piglets produce symptoms. However, caused has not been fully elucidated. Actin important component eukaryotic serves first obstacle pathogens morphological structure function depend on skeleton. Therefore, exploring injury induced from perspective only helps elucidate pathogenesis but also provides basis search targets. This report define mechanistic link between alterations pathways invading