HIV evades RNA interference directed at TAR by an indirect compensatory mechanism.
HIV evades RNA interference directed at TAR by an indirect compensatory mechanism.
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DOI：
10.1016/j.chom.2008.09.008
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发表时间：
2008-11-13
影响因子：
30.3
通讯作者：
Schaffer DV
中科院分区：
文献类型：
--
作者：
Leonard JN;Shah PS;Burnett JC;Schaffer DV
与许多病毒一样，艾滋病毒在受到选择性压力（包括免疫监视或抗逆转录病毒药物的施用）时会迅速进化。病毒通常通过突变目标蛋白质来获得抵抗力。因此，当 HIV 被针对病毒 RNA 的 RNA 干扰 (RNAi) 抑制时，它会通过在目标区域获得突变而逃脱，从而规避 RNAi 介导的抑制，同时保留必要的病毒功能。然而，当我们针对病毒 TAR 发夹中的一个新靶标进行 RNAi 时，HIV 并没有使靶位点发生突变，而该靶标是无法在不严重损害病毒复制的情况下进行改变的。相反，分离出了一些通过上调病毒转录来间接补偿抗病毒活性的突变。这代表了一种新机制，病毒可以通过该机制调整病毒转录调控，作为补偿病毒抑制的间接机制。
Like many viruses, HIV can rapidly evolve when placed under selective pressure, including immune surveillance or the administration of antiretroviral drugs. The virus typically acquires resistance by mutating the targeted proteins. Accordingly, when HIV has been suppressed with RNA interference (RNAi) directed against viral RNAs, it has escaped by acquiring mutations at the target region that circumvent RNAi-mediated inhibition while conserving necessary viral functions. However, when we directed RNAi against a novel target in the viral TAR hairpin, which cannot be altered without severely impairing viral replication, HIV did not mutate the target site. Instead several mutations that indirectly compensated for the antiviral activity through upregulation of viral transcription were isolated. This represents a novel mechanism by which viruses can tune viral transcriptional regulation as an indirect mechanism to compensate for viral suppression.
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影响因子：
46.9
作者：
Haasnoot J;Westerhout EM;Berkhout B
通讯作者：
Berkhout B
影响因子：
5.4
作者：
DELASSUS, S;CHEYNIER, R;WAINHOBSON, S
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WAINHOBSON, S
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作者：
KATO, H;HORIKOSHI, M;ROEDER, RG
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ROEDER, RG
影响因子：
5.4
作者：
Leonard, JN;Schaffer, DV
通讯作者：
Schaffer, DV
影响因子：
56.9
作者：
DEACON, NJ;TSYKIN, A;MILLS, J
通讯作者：
MILLS, J