title: Inhibition of cyclophilin A suppresses H2O2-enhanced replication of HCMV through the p38 MAPK signaling pathway.
abstract: Human cytomegalovirus (HCMV) infection can be accelerated by intracellular and extracellular hydrogen peroxide (H2O2) stimulation, mediated by the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. However, it remains unknown whether host gene expression is involved in H2O2-upregulated HCMV replication. Here, we show that the expression of the host gene, cyclophilin A (CyPA), could be facilitated by treatment with H2O2 in a dose-dependent manner. Experiments with CyPA-specific siRNA, or with cyclosporine A, an inhibitor of CyPA, confirmed that H2O2-mediated upregulation of HCMV replication is specifically mediated by upregulation of CyPA expression. Furthermore, depletion or inhibition of CyPA reduced H2O2-induced p38 activation, consistent with that of H2O2-upregulated HCMV lytic replication. These results show that H2O2 is capable of activating ROS-CyPA-p38 MAPK interactions to enhance HCMV replication.
authors.affiliation: Beijing Institute of Transfusion Medicine China; Beijing Key Laboratory of Blood Safety and Supply Technologies China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Beijing Institute of Transfusion Medicine China; Beijing Key Laboratory of Blood Safety and Supply Technologies China.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: Beijing Institute of Transfusion Medicine China; Beijing Key Laboratory of Blood Safety and Supply Technologies China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Deng
authors.affiliation: Beijing Institute of Transfusion Medicine China; Beijing Key Laboratory of Blood Safety and Supply Technologies China.
authors.forename: Liping
authors.initials: L
authors.lastname: Lv
authors.affiliation: Beijing Institute of Transfusion Medicine China; Beijing Key Laboratory of Blood Safety and Supply Technologies China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.affiliation: Beijing Institute of Transfusion Medicine China; Beijing Key Laboratory of Blood Safety and Supply Technologies China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Beijing Institute of Transfusion Medicine China; Beijing Key Laboratory of Blood Safety and Supply Technologies China.
authors.forename: Xipeng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Beijing Institute of Transfusion Medicine China; Beijing Key Laboratory of Blood Safety and Supply Technologies China.
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Transfusion Medicine China; Beijing Key Laboratory of Blood Safety and Supply Technologies China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Xu
keywords: H2O2; cyclophilin A; cytomegalovirus; p38 MAPK; viral replication