Phylogenetic Insights into the Functional Relationship between Primate Lentiviral Reverse Transcriptase and Accessory Proteins Vpx/Vpr.
Phylogenetic Insights into the Functional Relationship between Primate Lentiviral Reverse Transcriptase and Accessory Proteins Vpx/Vpr.
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DOI：
10.3389/fmicb.2016.01655
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发表时间：
2016
影响因子：
5.2
通讯作者：
Nomaguchi M
中科院分区：
文献类型：
--
作者：
Sakai Y;Doi N;Miyazaki Y;Adachi A;Nomaguchi M
逆转录在感染细胞中合成病毒DNA的效率极大地影响逆转录病毒的复制动力学。然而，在非分裂细胞如静息T细胞和终末分化的巨噬细胞中的病毒复制受到命名为SAMHD 1（无菌α基序和含HD结构域的蛋白1）的宿主抗病毒因子的有效和动力学限制。SAMHD 1减少细胞脱氧核苷三磷酸（dNTP）池并影响病毒逆转录步骤。人类免疫缺陷病毒2型（HIV-2）和一些猿猴免疫缺陷病毒（SIV）具有Vpx或Vpr，可有效降解SAMHD 1。有趣的是，来自HIV-1的不编码抗SAMHD 1蛋白的逆转录酶（RT）先前已被证明独特地表现出高酶活性。因此，假设一些病毒可能已经获得或失去了特异性RT特性以更好地适应非分裂细胞中面临的低dNTP环境并非不合理。这种适应过程可能与病毒对SAMHD 1的拮抗能力有关。在这份报告中，我们问这样的适应性事件是否可以推断从Vpx/Vpr和RT系统发育树覆盖SAMHD 1降解能力的Vpx/Vpr和RT的动力学特性。结果两棵树显示出基本相似的聚类模式，因此建议RT和Vpx/Vpr的属性可以连接。换句话说，HIV/SIV可能拥有自己的RT蛋白，以充分反应靶细胞中的各种dNTP环境。
The efficiency of reverse transcription to synthesize viral DNA in infected cells greatly influences replication kinetics of retroviruses. However, viral replication in non-dividing cells such as resting T cells and terminally differentiated macrophages is potently and kinetically restricted by a host antiviral factor designated SAMHD1 (sterile alpha motif and HD-domain containing protein 1). SAMHD1 reduces cellular deoxynucleoside triphosphate (dNTP) pools and affects viral reverse transcription step. Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs) have Vpx or Vpr to efficiently degrade SAMHD1. Interestingly, the reverse transcriptase (RT) derived from HIV-1 that encodes no anti-SAMHD1 proteins has been previously demonstrated to uniquely exhibit a high enzymatic activity. It is thus not irrational to assume that some viruses may have acquired or lost the specific RT property to better adapt themselves to the low dNTP environments confronted in non-dividing cells. This adaptation process may probably be correlated with the SAMHD1-antagonizing ability by viruses. In this report, we asked whether such adaptive events can be inferable from Vpx/Vpr and RT phylogenetic trees overlaid with SAMHD1-degrading capacity of Vpx/Vpr and with kinetic characteristics of RT. Resultant two trees showed substantially similar clustering patterns, and therefore suggested that the properties of RT and Vpx/Vpr can be linked. In other words, HIV/SIVs may possess their own RT proteins to adequately react to various dNTP circumstances in target cells.