FEEDBACK-REGULATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EXPRESSION BY THE REV PROTEIN
FEEDBACK-REGULATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EXPRESSION BY THE REV PROTEIN
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DOI：
10.1128/jvi.64.8.3734-3741.1990
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发表时间：
1990-08-01
影响因子：
5.4
通讯作者：
PAVLAKIS, GN
中科院分区：
文献类型：
--
作者：
FELBER, BK;DRYSDALE, CM;PAVLAKIS, GN
REV是人类免疫缺陷病毒1型(HIV-1)的重要调节蛋白，影响某些病毒mRNAs的运输和半衰期。REV通过一种独特的元件--REV反应元件(RRE)发挥其功能，该元件位于HIV-1的包膜区域内。以前已经证明，REV影响含RRE和不含RRE的mRNAs的相对水平。我们研究了REV对三组不同的小的、多个剪接的mRNAs表达的影响，这些mRNAs缺乏RRE序列，编码调节蛋白TAT、REV和Nef。为了监测TAT、TeV和nef的mRNAs，我们产生了区分它们的特异的S1核酸酶图谱探针。对所有产生TAT、REV和Nef的mRNA物种的分析表明，它们的水平都受到REV的协同调节，在没有REV蛋白的情况下它们的表达增加，在REV的存在下它们的表达下调。免疫沉淀法测定了相应的蛋白，它们的水平与RNA的水平一致。这些结果验证了REV是一个通用调控因子的模型，该模型间接影响所有多重剪接的mRNAs，影响程度相似。因此，Rev向下调节自身的表达以及Tat和Nef的表达。
Rev is an essential regulatory protein of the human immunodeficiency virus type 1 (HIV-1) that affects the transport and half-life of certain viral mRNAs. Rev exerts its function via a unique element, the Rev-responsive element (RRE), located within the env region of HIV-1. It has been previously demonstrated that Rev affects the relative levels of RRE-containing and RRE-lacking mRNAs. We have studied the effects of Rev on the expression of the three different groups of small, multiply spliced mRNAs that lack the RRE sequence and encode the regulatory proteins Tat, Rev and Nef. To monitor that tat, tev, and nef mRNAs we generated specific S1 nuclease mapping probes that distinguish among them. Analysis of all the mRNA species producing Tat, Rev, and Nef revealed that their levels are coordinately regulated by Rev. They are increased in the absence of Rev protein and are down regulated in the presence of Rev. The corresponding proteins were measured by immunoprecipitations, and their levels are in agreement with the RNA levels. These results verify the model proposing that Rev is a general regulator indirectly affecting all the multiply spliced mRNAs to a similar extent. Therefore, Rev down regulates its own expression and the expression of Tat and Nef.