Owen S M, Lal R B, Ikeda R A
HIV and Retrovirus Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
J Virol. 1998 Jun;72(6):5279-84. doi: 10.1128/JVI.72.6.5279-5284.1998.
Unlike most other characterized retroviruses, there is little published information on the biochemical properties of human T-lymphotropic virus type 1 (HTLV-1) reverse transcriptase (RT). Specifically, no reports of a cloned functional RT enzyme have been published. Since the RT enzyme is an essential component of the virus, our objective was to clone, express, and purify a functional RT enzyme from HTLV-1. Our approach was to clone and express a protein of approximately 60 to 65 kDa that we hypothesized would correspond to the RT region encoded by the pol reading frame. The predicted region encoding the RT enzyme comprised nucleotides 2617 to 4312 of the HTLV-1 MT-2 isolate. A putative RT gene was obtained by PCR and was ligated into various prokaryotic expression vectors. A novel cloning approach allowed us to generate a stable clone in the prokaryotic expression vector pGEX-4T-1 and produce a recombinant protein of approximately 60 to 65 kDa. The partially purified protein displays RT activity in both amplification RT (AMP-RT) assays and traditional RT assays. This is the first report of a cloned protein from HTLV-1 which displays RT activity and is the first step in the characterization of HTLV-1 RT.
与大多数其他已鉴定的逆转录病毒不同,关于1型人类嗜T淋巴细胞病毒(HTLV-1)逆转录酶(RT)的生化特性,公开的信息很少。具体而言,尚未发表有关克隆的功能性RT酶的报道。由于RT酶是该病毒的重要组成部分,我们的目标是从HTLV-1中克隆、表达并纯化一种功能性RT酶。我们的方法是克隆并表达一种约60至65 kDa的蛋白质,我们推测该蛋白质与pol阅读框编码的RT区域相对应。预测的编码RT酶的区域包括HTLV-1 MT-2分离株的核苷酸2617至4312。通过PCR获得了一个推定的RT基因,并将其连接到各种原核表达载体中。一种新颖的克隆方法使我们能够在原核表达载体pGEX-4T-1中产生稳定的克隆,并产生一种约60至65 kDa的重组蛋白。部分纯化的蛋白在扩增RT(AMP-RT)试验和传统RT试验中均显示出RT活性。这是关于来自HTLV-1的具有RT活性的克隆蛋白的首次报道,也是HTLV-1 RT表征的第一步。