Proteasome inhibitor bortezomib inhibits replication of Enterovirus D68 / 中华实验和临床病毒学杂志

ABSTRACT

Objective@#To investigate the inhibitory effect of bortezomib (PS-341) on enterovirus replication.@*Methods@#The methyl thiazolyl tetrazolium (MTT) assay was used to value cell viability in response to PS-341 treatment. The protein and viral gene mRNAs were measured by real-time quantitative PCR (qRT-PCR).@*Results@#Our result show that after enterovirus (EV)-D68 or coxsackievirus B3 (CV-B3) infected cells were treated with PS-341, compared with the control group, the inhibition rate of the intracellular viral RNA reached 50%~70% or 60%~90%. PS-341 was added after RD cells were infectd with EV-D68, the intracellular virus titer was down-regulated by 90.23% and 83.40% in the supernatant, the intracellular virus titer was down-regulated by 93% and 90% in the supernatant and in RD cells. PS-341 had no effect on virus adsorption and importing. The cells were treated with PS-341 and apoptosis-inhibiting agent Ac-YVAD-CHO, the viral RNA replication inhibition rate reached 10%-30%, and the expression of viral protein was increased, which indicated that the inhibitory effect of PS-341 on viral replication was attenuated.@*Conclusions@#According to the result of the study, PS-341 could reduce apoptosis by regulating the proteasome pathway, inhibiting the gene replication and assemble, without effect on virus adsorption, entry and release. In addition, PS-341 also inhibited the replication of CV-B3 in cells, which suggest that PS-341 has a broad spectrum anti-EVs effects.