Demonstration of a novel HIV-1 restriction phenotype from a human T cell line.
Demonstration of a novel HIV-1 restriction phenotype from a human T cell line.
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DOI：
10.1371/journal.pone.0002796
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发表时间：
2008-07-30
期刊：
影响因子：
3.7
通讯作者：
Zheng, Yong-Hui
中科院分区：
文献类型：
--
作者：
Han, Yanxing;Wang, Xiaojun;Dang, Ying;Zheng, Yong-Hui
尽管逆转录病毒可以侵入宿主细胞，但只有在病毒抵消不同类型宿主限制因子的抑制后才能建立有效感染。 Fv1、APOBEC3G/F、TRIM5α、ZAP 和 CD317 通过干扰病毒脱壳、逆转录、核输入、RNA 稳定性和释放来抑制不同逆转录病毒的复制。在人类中，虽然 APOBEC3G/3F 和 CD317 阻断 HIV-1 复制，但它们的抗病毒活性会被病毒蛋白 Vif 和 Vpu 中和。迄今为止，尚未发现人类基因能够在自然条件下有效阻断野生型HIV-1的复制。因此，鉴定这种基因产物对于艾滋病毒疗法的开发具有重要的医学意义。在这项研究中，我们发现了一种针对来自 CD4/CXCR4 双阳性人类 T 细胞系的野生型 HIV-1 的新型宿主限制。我们鉴定出一种 CEM 衍生细胞系 (CEM.NKR)，该细胞系对 HIV-1 感染具有高度抵抗力。与其他允许的人类 T 细胞系（例如 H9、A3.01 和 CEM-T4）相比，病毒产量减少了至少 1000 倍。重要的是，这种抵抗力在极高的感染复数下非常明显。进一步分析表明，HIV-1可以在CEM.NKR细胞中完成第一轮复制，但释放的病毒颗粒传染性较差。这些病毒体可以进入靶细胞，但无法启动逆转录。值得注意的是，这种限制表型也存在于 CEM.NKR 和 293T 异核体中。这些结果清楚地表明 CEM.NKR 细胞表达 HIV 抑制基因。这种新基因产物的进一步表征将揭示一种直接灭活野生型 HIV-1 的新抗逆转录病毒机制。
Although retroviruses may invade host cells, a productive infection can be established only after the virus counteracts inhibition from different types of host restriction factors. Fv1, APOBEC3G/F, TRIM5α, ZAP, and CD317 inhibit the replication of different retroviruses by interfering with viral uncoating, reverse transcription, nuclear import, RNA stability, and release. In humans, although APOBEC3G/3F and CD317 block HIV-1 replication, their antiviral activities are neutralized by viral proteins Vif and Vpu. So far, no human gene has been found to effectively block wild type HIV-1 replication under natural condition. Thus, identification of such a gene product would be of great medical importance for the development of HIV therapies. In this study, we discovered a new type of host restriction against the wild type HIV-1 from a CD4/CXCR4 double-positive human T cell line. We identified a CEM-derived cell line (CEM.NKR) that is highly resistant to productive HIV-1 infection. Viral production was reduced by at least 1000-fold when compared to the other permissive human T cell lines such as H9, A3.01, and CEM-T4. Importantly, this resistance was evident at extremely high multiplicity of infection. Further analyses demonstrated that HIV-1 could finish the first round of replication in CEM.NKR cells, but the released virions were poorly infectious. These virions could enter the target cells, but failed to initiate reverse transcription. Notably, this restriction phenotype was also present in CEM.NKR and 293T heterokaryons. These results clearly indicate that CEM.NKR cells express a HIV inhibitory gene(s). Further characterization of this novel gene product(s) will reveal a new antiretroviral mechanism that directly inactivates wild type HIV-1.
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影响因子：
64.8
作者：
Best, S;LeTissier, P;Stoye, JP
通讯作者：
Stoye, JP
影响因子：
4.8
作者：
Dang, Ying;Siew, Lai Mun;Zheng, Yong-Hui
通讯作者：
Zheng, Yong-Hui
影响因子：
4.8
作者：
Holmes, Rebecca K.;Koning, Fransje A.;Malim, Michael H.
通讯作者：
Malim, Michael H.
DOI：
10.1073/pnas.93.18.9606
发表时间：
1996-09-03
影响因子：
11.1
作者：
Li, Y;Bergeron, JJJM;Kang, CY
通讯作者：
Kang, CY
DOI：
10.1073/pnas.212400099
发表时间：
2002-10-15
影响因子：
11.1
作者：
Münk, C;Brandt, SM;Landau, NR
通讯作者：
Landau, NR