Inhibition of human cytomegalovirus replication by tricin is associated with depressed CCL2 expression

We previously reported that treatment with tricin (4′,5,7-trihydroxy-3′,5′-dimethoxyflavone) after human cytomegalovirus (HCMV) infection significantly suppressed both infectious virion production and HCMV replication in human embryonic lung fibroblast (HEL) cells. Moreover, we recently demonstrated that HCMV infection can increase the expression of CC-motif ligand 2 (CCL2/MCP-1) and of CCR2, a CCL2-specific receptor, effects that can in turn enhance HCMV infection and replication. Hence, we here examined whether the CCL2-CCR2 axis is involved in the anti-HCMV effects of tricin in HEL cells. Tricin exposure yielded dose-dependent decreases in the accumulation of transcripts for the HCMV immediate early gene and the DNA polymerase gene in HCMV-infected cells, along with decreased production of infectious HCMV. Concomitantly, tricin caused dose-dependent attenuation of HCMV infection-induced up-regulation of expression of CCL2 and CCR2 mRNAs and of CCL2 protein. Moreover, CCL2 reversed tricin-mediated inhibition of HCMV virion production in a dose-dependent manner. Thus, tricin appears to exert anti-HCMV activity by depressing CCL2 expression.