Wang Pengfei, Qu Xiying, Zhou Xin, Shen Yinzhong, Ji Haiyan, Fu Zheng, Deng Junxiao, Lu Panpan, Yu Wenbo, Lu Hongzhou, Zhu Huanzhang
State Key Laboratory of Genetic Engineering, and Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, School of Life Sciences, Fudan University, Shanghai, China.
Department of Infectious Diseases, and Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Virology. 2015 Dec;486:228-38. doi: 10.1016/j.virol.2015.09.016. Epub 2015 Oct 27.
Understanding the mechanism of HIV-1 latency is crucial to the viral reservoir eradication. Human cellular miRNAs can modulate HIV-1 expression by targeting of viral RNAs or host gene transcripts. To identify miRNAs modulating HIV-1 latency, we determined the miRNA expression profiles of HIV-1 latently infected and productively infected cells by microarray and qRT-PCR. Among the differentially expressed miRNAs, miR-196b and miR-1290 targeted the 3' untranslated region of HIV-1 and affected its expression. Ectopic expression of these two miRNAs efficiently suppressed HIV-1 production and infectivity. Specific inhibitors of these miRNAs substantially counteracted their effects on HIV-1, as measured either as viral production and infectivity in HEK-293T cells or as HIV-1 RNA expression or viral production in cells isolated from HIV-1-infected individuals. Our study emphasizes the role of cellular miRNAs in HIV-1 latency regulation, and it suggests that inhibitors of miR-196b and miR-1290 could be used to activate latent HIV-1.
了解HIV-1潜伏机制对于消除病毒储存库至关重要。人类细胞微小RNA（miRNA）可通过靶向病毒RNA或宿主基因转录本来调节HIV-1的表达。为了鉴定调节HIV-1潜伏的miRNA，我们通过微阵列和定量逆转录聚合酶链反应（qRT-PCR）确定了HIV-1潜伏感染细胞和高效感染细胞的miRNA表达谱。在差异表达的miRNA中，miR-196b和miR-1290靶向HIV-1的3'非翻译区并影响其表达。这两种miRNA的异位表达有效抑制了HIV-1的产生和感染性。这些miRNA的特异性抑制剂显著抵消了它们对HIV-1的影响，这在HEK-293T细胞中通过病毒产生和感染性来衡量，或者在从HIV-1感染个体分离的细胞中通过HIV-1 RNA表达或病毒产生来衡量。我们的研究强调了细胞miRNA在HIV-1潜伏调节中的作用，并表明miR-196b和miR-1290的抑制剂可用于激活潜伏的HIV-1。
