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 (Cy PA ), could be facilitated by treatment with H 2 O 2 in a dose‐dependent manner. Experiments with Cy PA ‐specific si RNA , or with cyclosporine A, an inhibitor of Cy PA , confirmed that H 2 O 2 ‐mediated upregulation of HCMV replication is specifically mediated by upregulation of Cy PA expression. Furthermore, depletion or inhibition of Cy PA 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 ‐Cy PA –p38 MAPK interactions to enhance HCMV replication.
【저자키워드】 viral replication, cytomegalovirus, cyclophilin A, H2O2, p38