Overexpression of CBX4 facilitated EV71 replication by increasing viral protein levels and titers, while CBX4 knockdown and SUMOylation inhibitor 2-D08 significantly suppressed EV71 replication in infected human cell lines.
CBX4 facilitates EV71 replication by mediating SUMOylation and stabilization of the 3D polymerase, suggesting SUMOylation inhibitors like 2-D08 as potential antiviral therapies.
p-value: p=Observed significance: for viral titer increase with CBX4 overexpression at 24 h, CBX4 knockdown decreased VP1 and 3C protein levels and viral titers with p < 0.05 to p < 0.001; 2-D08 reduced viral proteins and titers dose-dependently with p < 0.05 to p < 0.001
Enterovirus 71 (EV71) is a primary etiological agent of hand-foot-mouth disease (HFMD) in children under 5 years of age and can cause severe neurological disorders even death. Therefore, elucidating the infection mechanism and pathogenicity of EV71 is essential for developing more effective and targeted therapies to prevent and control EV71-associated diseases. Here, we initially reported that the SUMO E3 ligase CBX4 is important for EV71 replication. Furthermore, we found that CBX4 interacts with the EV71 3D polymerase, and overexpression of CBX4 significantly extends the half-life of 3D, whereas knockdown of CBX4 reduces the stability of 3D protein. Subsequent investigations demonstrated that CBX4 mediates both SUMOylation and ubiquitination modifications of 3D, and treatment with protein SUMOylation inhibitor 2-D08 remarkably depresses EV71 replication and the expression of ectopically transfected 3D. The regulatory role of CBX4 and the effect of 2-D08 were also observed in other enteroviruses, including coxsackievirus B3 (CVB3) and poliovirus 1 (PV1). These findings revealed that CBX4 facilitates EV71 infection through inducing SUMOylation and stabilization of 3D polymerase, hinting its potential as a novel target for antiviral development.
Su et al. (Wed,) conducted a other in Cell lines infected with Enterovirus 71 (EV71). CBX4 overexpression or knockdown; SUMOylation inhibitor 2-D08 vs. Vector control or vehicle control was evaluated on EV71 viral replication assessed by VP1 and 3C protein levels, VP1 mRNA expression, viral dsRNA expression, and viral titers in cell supernatants (p=Observed significance: for viral titer increase with CBX4 overexpression at 24 h, CBX4 knockdown decreased VP1 and 3C protein levels and viral titers with p < 0.05 to p < 0.001; 2-D08 reduced viral proteins and titers dose-dependently with p < 0.05 to p < 0.001). Overexpression of CBX4 facilitated EV71 replication by increasing viral protein levels and titers, while CBX4 knockdown and SUMOylation inhibitor 2-D08 significantly suppressed EV71 replication in infected human cell lines.