Determination of the protease cleavage site repertoire--the RNase H but not the RT domain is essential for foamy viral protease activity.

Determination of the protease cleavage site repertoire--the RNase H but not the RT domain is essential for foamy viral protease activity.
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确定蛋白酶裂解位点库 - RNase H 而不是 RT 结构域对于泡沫病毒蛋白酶活性至关重要

DOI:
10.1016/j.virol.2014.02.013
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
J. Bodem
J. Bodem
中科院分区:
医学3区
文献类型:
--
作者:
Spannaus;J. Bodem

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与正转录酶病毒不同,泡沫病毒蛋白酶仅作为蛋白酶-逆转录酶融合蛋白具有活性,并且需要病毒RNA才能激活。泡沫状病毒蛋白的成熟似乎局限于Gag和Pol的单个裂解位点。我们提供的证据表明,未经处理的Gag是最佳感染性所必需的,这在逆转录病毒中是独一无二的。通过对Gag和Pol裂解位点序列的分析,发现其与慢病毒具有较高的相似性。我们发现位置P2和P2是不变的,Gag和Pol裂解位点的处理效率相似。RNase H结构域对蛋白酶活性至关重要,但在功能上可以被其他逆转录病毒的RNase H结构域所取代。因此,RNase H结构域可能参与了蛋白酶二聚体的稳定,而RT结构域对于RNA依赖性蛋白酶的激活至关重要。
In contrast to orthoretroviruses, the foamy virus protease is only active as a protease-reverse transcriptase fusion protein and requires viral RNA for activation. Maturation of foamy viral proteins seems to be restricted to a single cleavage site in Gag and Pol. We provide evidence that unprocessed Gag is required for optimal infectivity, which is unique among retroviruses. Analyses of the cleavage site sequences of the Gag and Pol cleavage sites revealed a high similarity compared to those of Lentiviruses. We show that positions P2׳ and P2 are invariant and that Gag and Pol cleavage sites are processed with similar efficiencies. The RNase H domain is essential for protease activity, but can functionally be substituted by RNase H domains of other retroviruses. Thus, the RNase H domain might be involved in the stabilization of the protease dimer, while the RT domain is essential for RNA dependent protease activation.
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