Human immunodeficiency virus type 1 escape from RNA interference
Human immunodeficiency virus type 1 escape from RNA interference
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DOI：
10.1128/jvi.77.21.11531-11535.2003
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发表时间：
2003-11-01
影响因子：
5.4
通讯作者：
Ramratnam, B
中科院分区：
文献类型：
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作者：
Boden, D;Pusch, O;Ramratnam, B
短干扰RNA（siRNA）对mRNA的序列特异性降解允许选择性抑制对人类免疫缺陷病毒I型（HIV-1）复制至关重要的病毒蛋白。本研究的目的是表征病毒特异性RNA干扰（RNAi）在稳定表达靶向HIV-1反式激活蛋白基因达特的短发夹RNA（shRNA）的细胞系中的效力和持久性。我们发现达特shRNA的抗病毒活性由于在shRNA靶区域中存在点突变的病毒准种的出现而被取消。我们的研究结果表明，为了使RNAi持久地抑制HIV-1复制，可能有必要靶向病毒基因组的高度保守区域。或者，类似于目前的抗病毒药物治疗范例，需要开发靶向病毒基因组不同区域的表达多个siRNA的DNA构建体，从而降低产生逃逸突变体的可能性。
Sequence-specific degradation of mRNA by short interfering RNA (siRNA) allows the selective inhibition of viral proteins that are critical for human immunodeficiency virus type I (HIV-1) replication. The aim of this study was to characterize the potency and durability of virus-specific RNA interference (RNAi) in cell lines that stably express short hairpin RNA (shRNA) targeting the HIV-1 transactivator protein gene tat. We found that the antiviral activity of tat shRNA was abolished due to the emergence of viral quasispecies harboring a point mutation in the shRNA target region. Our results suggest that, in order for RNAi to durably suppress HIV-1 replication, it may be necessary to target highly conserved regions of the viral genome. Alternatively, similar to present antiviral drug therapy paradigms, DNA constructs expressing multiple siRNAs need to be developed that target different regions of the viral genome, thereby reducing the probability of generating escape mutants.