Inhibition of cyclophilin A suppresses H(2)O(2)‐enhanced replication of HCMV through the p38 MAPK signaling pathway

Human cytomegalovirus (HCMV) infection can be accelerated by intracellular and extracellular hydrogen peroxide (H(2)O(2)) 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 H(2)O(2)‐upregulated HCMV replication. Here, we show that the expression of the host gene, cyclophilin A (CyPA), could be facilitated by treatment with H(2)O(2) in a dose‐dependent manner. Experiments with CyPA‐specific siRNA, or with cyclosporine A, an inhibitor of CyPA, confirmed that H(2)O(2)‐mediated upregulation of HCMV replication is specifically mediated by upregulation of CyPA expression. Furthermore, depletion or inhibition of CyPA reduced H(2)O(2)‐induced p38 activation, consistent with that of H(2)O(2)‐upregulated HCMV lytic replication. These results show that H(2)O(2) is capable of activating ROS‐CyPA–p38 MAPK interactions to enhance HCMV replication.