Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, China.
Antiviral Res. 2011 Mar;89(3):219-26. doi: 10.1016/j.antiviral.2011.01.008. Epub 2011 Feb 1.
MicroRNAs (miRNAs) are short non-coding RNAs that negatively modulate gene expression at the post-transcriptional level and are known to be involved in the cross-talk between the host and virus. Using a standard plaque assay and real-time PCR method, we found that ectopic expression of miR-101 could significantly suppress herpes simplex virus-1 (HSV-1) replication, and that blocking endogenous miR-101 could increase viral progeny without affecting cell viability. Bioinformatics analysis indicates the 3' untranslated region (UTR) of mitochondrial ATP synthase subunit beta (ATP5B) has a putative binding site for miR-101. MiR-101 can directly bind to ATP5B 3'UTR and negatively regulate ATP5B expression. Using a RNA interference technique, knockdown of ATP5B significantly inhibited HSV-1 replication, indicating that ATP5B functions as a pro-viral factor. The ectopic expression of ATP5B lacking the 3'UTR could override the suppressive effect of miR-101 on HSV-1 replication. A concordant inverse correlation between miR-101 and ATP5B was observed in HSV-1-infected HeLa cells. Up-regulation of miR-101 expression may play a role in repressing productive HSV-1 replication by targeting ATP5B. Exploring the role of host-encoded miRNA in the regulation of viral infection would enable us to better understand the intricate networks of host-pathogen interactions.
微小 RNA（miRNAs）是短的非编码 RNA，在转录后水平上负调控基因表达，已知其参与宿主与病毒之间的串扰。我们使用标准的噬菌斑测定法和实时 PCR 方法发现，miR-101 的异位表达可显著抑制单纯疱疹病毒-1（HSV-1）的复制，而阻断内源性 miR-101 可以增加病毒子代而不影响细胞活力。生物信息学分析表明线粒体 ATP 合酶亚基β（ATP5B）的 3'非翻译区（UTR）具有 miR-101 的假定结合位点。miR-101 可以直接结合到 ATP5B 3'UTR 并负调控 ATP5B 的表达。使用 RNA 干扰技术，敲低 ATP5B 显著抑制 HSV-1 复制，表明 ATP5B 作为促病毒因子发挥作用。缺少 3'UTR 的 ATP5B 的异位表达可以克服 miR-101 对 HSV-1 复制的抑制作用。在 HSV-1 感染的 HeLa 细胞中观察到 miR-101 和 ATP5B 之间呈一致的负相关。miR-101 表达的上调可能通过靶向 ATP5B 来抑制有活力的 HSV-1 复制。探索宿主编码 miRNA 在病毒感染调控中的作用可以使我们更好地理解宿主-病原体相互作用的复杂网络。
