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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. [ABSTRACT FROM AUTHOR]

We previously revealed that human cytomegalovirus (HCMV) infection can cause aberrant expression of the chemokine IL-8/CXCL8. We first examined the effects of HCMV infection on the expression of another chemokine, CCL2. HCMV infection induced CCL2 expression at the mRNA and protein levels in human embryonic lung fibroblasts cells (HEL). Moreover, HCMV induced the mRNA expression of CCR2, a specific receptor for CCL2. CCL2 siRNA treatment reduced HCMV virion production, and this reduction was reversed by the addition of CCL2. We further observed that CCL2 siRNA, but not control siRNA, reduced the expression of HCMV immediate early gene (IE1) and HCMV UL54 gene (DNA polymerase) in a dose-dependent manner. Thus, HCMV infection is able to activate the CCL2–CCR2 interactions to further enhance HCMV infection and/or replication. [ABSTRACT FROM AUTHOR]