Proteasome inhibitor bortezomib inhibits replication of Enterovirus D68
10.3760/cma.j.issn.1003-9279.2019.03.003
- VernacularTitle: 蛋白酶体抑制剂PS-341抑制人肠道病毒D68复制研究
- Author:
Keke ZHANG
1
;
Dong XIA
2
;
Sihua LIU
1
;
Zhenwei ZHOU
1
;
Jun HAN
2
;
Tao WANG
1
Author Information
1. School of Life Sciences, Tianjin University, Tianjin 300110, China
2. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, State Key Laboratory of Infectious Disease Prevention and Cotrol, Collaborative Innovation Center for Diagnosis and Treatment of Infections Disease, Beijing 102206, China
- Publication Type:Journal Article
- Keywords:
EV-D68;
CV-B3;
PS-341;
Apoptosis
- From:
Chinese Journal of Experimental and Clinical Virology
2019;33(3):236-243
- CountryChina
- Language:Chinese
-
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.