The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
Department of Virology, Institute for Medical Microbiology and Hygiene, Albert-Ludwigs-Universitat, Freiburg, Germany.
PLoS Pathog. 2014 Feb 27;10(2):e1003963. doi: 10.1371/journal.ppat.1003963. eCollection 2014 Feb.
The human cytomegalovirus (HCMV) is extremely prevalent in the human population. Infection by HCMV is life threatening in immune compromised individuals and in immune competent individuals it can cause severe birth defects, developmental retardation and is even associated with tumor development. While numerous mechanisms were developed by HCMV to interfere with immune cell activity, much less is known about cellular mechanisms that operate in response to HCMV infection. Here we demonstrate that in response to HCMV infection, the expression of the short form of the RNA editing enzyme ADAR1 (ADAR1-p110) is induced. We identified the specific promoter region responsible for this induction and we show that ADAR1-p110 can edit miR-376a. Accordingly, we demonstrate that the levels of the edited-miR-376a (miR-376a(e)) increase during HCMV infection. Importantly, we show that miR-376a(e) downregulates the immune modulating molecule HLA-E and that this consequently renders HCMV infected cells susceptible to elimination by NK cells.
人巨细胞病毒（HCMV）在人类中极为普遍。HCMV 感染对免疫功能低下的个体是致命的，而在免疫功能正常的个体中，它可导致严重的出生缺陷、发育迟缓，甚至与肿瘤发展有关。尽管 HCMV 开发了许多机制来干扰免疫细胞的活性，但对于细胞应对 HCMV 感染的机制却知之甚少。在这里，我们证明在 HCMV 感染后，短型 RNA 编辑酶 ADAR1（ADAR1-p110）的表达被诱导。我们确定了负责这种诱导的特定启动子区域，并表明 ADAR1-p110 可以编辑 miR-376a。因此，我们证明在 HCMV 感染过程中，编辑后的 miR-376a（miR-376a(e)）水平增加。重要的是，我们表明 miR-376a(e)下调免疫调节分子 HLA-E，从而使 HCMV 感染的细胞易被 NK 细胞消除。
