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.

先前我们曾报道过用Tricin（4 '，5,7-trihydroxy-3 '，5 '巨细胞病毒（HCMV）感染后，β-二甲氧基黄酮）会显着抑制人胚肺成纤维细胞（HEL）细胞中感染性病毒粒子的产生和HCMV复制。此外，我们最近证明，HCMV感染可以增加CC-基序配体2（CCL2 / MCP-1）和CCR2（一种CCL2特异性受体）的表达，进而可以增强HCMV感染和复制。因此，我们在这里检查了CCL2-CCR2轴是否参与了HEL细胞中的Tricin的抗HCMV效应。Tricin暴露导致HCMV感染的细胞中HCMV立即早期基因和DNA聚合酶基因的转录物积累量呈剂量依赖性降低，同时传染性HCMV产量降低。随之而来的是，Tricin引起HCMV感染的剂量依赖性减弱，从而引起HCMV的表达上调。CCL2和CCR2 mRNA和CCL2蛋白。此外，CCL2以剂量依赖的方式逆转了Tricin介导的HCMV病毒粒子生产的抑制。因此，Tricin似乎通过抑制CCL2表达而发挥抗HCMV活性。