Human cytomegalovirus miR-UL36-5p inhibits apoptosis via downregulation of adenine nucleotide translocator 3 in cultured cells
Human cytomegalovirus miR-UL36-5p inhibits apoptosis via downregulation of adenine nucleotide translocator 3 in cultured cells
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人巨细胞病毒 miR-UL36-5p 通过下调培养细胞中的腺嘌呤核苷酸易位子 3 抑制细胞凋亡
DOI：
10.1007/s00705-015-2498-8
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发表时间：
2015-10-01
影响因子：
2.7
通讯作者：
Ruan, Qiang
中科院分区：
文献类型：
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作者：
Guo, Xin;Huang, Yujing;Ruan, Qiang
人巨细胞病毒（HCMV）编码至少26个microrna （miRNA）。HCMV利用这些mirna在感染期间调节自身基因以及宿主细胞的基因。有报道称，通过杂交PCR，一个细胞基因，溶质载体家族25，成员6 (SLC25A6)，也被称为腺嘌呤核苷酸转运子3 (ANT3)，被确定为hcmv-miR-UL36-5p的候选靶点。在本研究中，通过荧光素酶报告基因检测进一步证明ANT3是hcmv-miR-UL36-5p的直接靶点。western blotting证实，过表达hcmv-miR-UL36-5p可直接下调HEK293细胞、U373细胞和HELF细胞中ANT3蛋白的表达水平。此外，hcmv感染细胞显示ANT3蛋白水平下降。利用ANT3特异性小干扰RNA （siRNA）和hcmv-miR-UL36-5p抑制剂，我们发现hcmv-miR-UL36-5p在这些细胞中特异性地通过抑制ANT3表达来抑制细胞凋亡。这些结果表明，HCMV - mir - ul36 -5可能在实际的HCMV感染过程中发挥同样的作用，从而在宿主细胞和病毒之间建立平衡。
Human cytomegalovirus (HCMV) encodes at least 26 microRNAs (miRNA). These miRNAs are utilized by HCMV to regulate its own genes as well as the genes of the host cell during infection. It has been reported that a cellular gene, solute carrier family 25, member 6 (SLC25A6), which is also designated adenine nucleotide translocator 3 (ANT3), was identified as a candidate target of hcmv-miR-UL36-5p by hybrid PCR. In this study, ANT3 was further demonstrated to be a direct target of hcmv-miR-UL36-5p by luciferase reporter assays. The expression level of ANT3 protein was confirmed, by western blotting, to be directly downregulated by overexpression of hcmv-miR-UL36-5p in HEK293 cells, U373 cells and HELF cells. Moreover, HCMV-infected cells showed a decrease in the ANT3 protein level. Using ANT3-specific small interfering RNA (siRNA) and an inhibitor for hcmv-miR-UL36-5p, it was shown that inhibition of apoptosis by hcmv-miR-UL36-5p in these cells specifically occurred via inhibition of ANT3 expression. These results imply that hcmv-miR-UL36-5 may play the same role during actual HCMV infection in order to establish a balance between the host cell and the virus.