PDF(Pubmed)
Abstract：
MicroRNAs (miRNAs) play important roles in the control of HIV-1 infection. Here, we performed RNA-seq profiling of miRNAs and mRNAs expressed in CD4+ T lymphocytes upon HIV-1 infection. Our results reveal significant alterations in miRNA and mRNA expression profiles in infected relative to uninfected cells. One of the miRNAs markedly downregulated in infected cells is miRNA-26a. Among the putative targets of miRNA-26a are CD59 receptor transcripts, which are significantly upregulated in infected CD4+ T cells. The addition of miRNA-26a mimics to CD4+ T cells reduces CD59 at both the mRNA and surface protein levels, validating CD59 as a miRNA-26a target. Consistent with the reported inhibitory role of CD59 in complement-mediated lysis (CML), knocking out CD59 in CD4+ T cells renders both HIV-1-infected cells and progeny virions more prone to antibody-dependent CML (ADCML). The addition of miRNA-26a mimics to infected cells leads to enhanced sensitivity of progeny virions to ADCML, a condition linked to a reduction in CD59 packaging into released virions. Lastly, HIV-1-mediated downregulation of miRNA-26a expression is shown to be dependent on integrated HIV-1 expression but does not involve viral accessory proteins. Overall, these results highlight a novel mechanism by which HIV-1 limits ADCML by upregulating CD59 expression via miRNA-26a downmodulation.
摘要：
MicroRNAs(miRNAs)在HIV-1感染控制中发挥重要作用。这里,我们对HIV-1感染后CD4+T淋巴细胞中表达的miRNA和mRNA进行了RNA-seq分析.我们的结果表明，相对于未感染的细胞，感染的miRNA和mRNA表达谱发生了显着变化。在感染细胞中显著下调的miRNA之一是miRNA-26a。miRNA-26a的推定靶标是CD59受体转录本，在感染的CD4+T细胞中显著上调。添加miRNA-26a模拟CD4+T细胞在mRNA和表面蛋白水平上减少CD59，验证CD59作为miRNA-26a靶标。与报道的CD59在补体介导的裂解（CML）中的抑制作用一致，敲除CD4+T细胞中的CD59使得HIV-1感染的细胞和子代病毒粒子更容易发生抗体依赖性CML(ADCML).将miRNA-26a模拟物添加到受感染的细胞导致子代病毒体对ADCML的敏感性增强,一种与CD59包装减少到释放的病毒体中有关的情况。最后,显示HIV-1介导的miRNA-26a表达的下调依赖于整合的HIV-1表达,但不涉及病毒辅助蛋白。总的来说,这些结果突出了HIV-1通过miRNA-26a下调上调CD59表达来限制ADCML的新机制.
