Many viruses disrupt the host cell cycle to facilitate their own growth. We assessed the mechanism and function of enterovirus 71 (EV71), a primary causative agent for recent hand, foot, and mouth disease outbreaks, in manipulating cell cycle progression. Our results suggest that EV71 infection induces S-phase arrest in diverse cell types by preventing the cell cycle transition from the S phase into the G2/M phase. Similar results were observed for an alternate picornavirus, Coxsackievirus A16. Synchronization in S phase, but not G0/G1 phase or G2/M phase, promotes viral replication. Consistent with its ability to arrest cells in S phase, the expression of cyclin A2, CDK 2, cyclin E1, and cyclin B1 was regulated by EV71 through increasing transcription of cyclin E1, promoting proteasome-mediated degradation of cyclin A2 and regulating the phosphorylation of CDK 2. Finally, a non-structural protein of EV71, the RNA-dependent RNA polymerase 3D, was demonstrated to mediate S-phase cell cycle arrest. These findings suggest that EV71 induces S-phase cell cycle arrest in infected cells via non-structural protein 3D, which may provide favorable conditions for virus production.

Rheumatoid arthritis is a common systemic and autoimmune disease characterized by symmetrical and inflammatory destruction of distal joints. Its primary pathological characters are synovitis and vasculitis. Accumulating studies have implicated the critical role of non-coding RNAs (ncRNAs) in inflammation and autoimmune regulation, primarily including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). NcRNAs are significant regulators in distinct physiological and pathophysiological processes. Many validated non-coding RNAs have been identified as promising biomarkers for the diagnosis and treatment of RA. This review will shed some light on RA pathogenesis and be helpful for identifying potential ncRNA biomarkers for RA.

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