ADAR1 Facilitates HIV-1 Replication in Primary CD4+ T Cells.
ADAR1 Facilitates HIV-1 Replication in Primary CD4+ T Cells.
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DOI：
10.1371/journal.pone.0143613
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kuijpers TW
中科院分区：
文献类型：
--
作者：
Cuadrado E;Booiman T;van Hamme JL;Jansen MH;van Dort KA;Vanderver A;Rice GI;Crow YJ;Kootstra NA;Kuijpers TW
与静息的CD 4 + T细胞不同，活化的CD 4 +T细胞对人类免疫缺陷病毒1（HIV-1）的感染高度敏感。HIV-1感染T细胞和巨噬细胞而不激活核酸传感器和抗病毒I型干扰素应答。腺苷脱氨酶作用于RNA 1（ADAR 1）是一种RNA编辑酶，对几种RNA病毒显示抗病毒活性。ADAR 1突变导致自身免疫性疾病Aicardi-Goutieères综合征（AGS）。这种疾病的特征是干扰素刺激的基因反应的不适当激活。在这里，我们表明，HIV-1的复制，在ADAR 1缺陷的CD 4 +T淋巴细胞从AGS患者，在蛋白质翻译的水平被阻止。此外，病毒蛋白质合成阻断伴随着干扰素刺激基因的激活。Jurkat细胞中ADAR 1的RNA沉默也抑制了HIV-1蛋白的合成。我们的数据支持HIV-1需要ADAR 1才能在人CD 4 +T细胞中有效复制。
Unlike resting CD4+ T cells, activated CD4+T cells are highly susceptible to infection of human immunodeficiency virus 1 (HIV-1). HIV-1 infects T cells and macrophages without activating the nucleic acid sensors and the anti-viral type I interferon response. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that displays antiviral activity against several RNA viruses. Mutations in ADAR1 cause the autoimmune disorder Aicardi-Goutieères syndrome (AGS). This disease is characterized by an inappropriate activation of the interferon-stimulated gene response. Here we show that HIV-1 replication, in ADAR1-deficient CD4+T lymphocytes from AGS patients, is blocked at the level of protein translation. Furthermore, viral protein synthesis block is accompanied by an activation of interferon-stimulated genes. RNA silencing of ADAR1 in Jurkat cells also inhibited HIV-1 protein synthesis. Our data support that HIV-1 requires ADAR1 for efficient replication in human CD4+T cells.