Inhibition of human cytomegalovirus replication by tricin is associated with depressed CCL2 expression
Inhibition of human cytomegalovirus replication by tricin is associated with depressed CCL2 expression
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DOI：
10.1016/j.antiviral.2017.09.018
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发表时间：
2017-12-01
影响因子：
7.6
通讯作者：
Murayama, Tsugiya
中科院分区：
文献类型：
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作者：
Akai, Yumiko;Sadanari, Hidetaka;Murayama, Tsugiya
我们之前报道了在人巨细胞病毒（HCMV）感染后用tricin（4',5,7-三羟基-3',5'-二甲氧基黄酮）治疗可显著抑制人胚胎肺成纤维细胞（HEL）中感染性病毒粒子的产生和HCMV的复制。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 （CCL2特异性受体）的表达，这种作用反过来可以增强HCMV感染和复制。因此，我们在此研究CCL2-CCR2轴是否参与tricin在HEL细胞中的抗hcmv作用。Tricin暴露导致HCMV感染细胞中HCMV即时早期基因和DNA聚合酶基因转录物积累呈剂量依赖性减少，同时感染性HCMV产生减少。同时，tricin引起HCMV感染的剂量依赖性衰减，诱导CCL2和CCR2 mrna以及CCL2蛋白表达上调。此外，CCL2以剂量依赖的方式逆转了tricin介导的HCMV病毒颗粒产生的抑制。因此，tricin似乎通过抑制CCL2表达来发挥抗hcmv活性。
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.