宿主因子MOV10抑制XMRV复制的机制研究
发布时间：2018-11-13 16:11
【摘要】：异嗜性鼠白血病病毒相关病毒(XMRV)是新发现的一种具有完全复制能力的γ逆转录病毒。早期研究报道XMRV可能与人类疾病前列腺癌、慢性疲劳综合症(CFS)有关,但随后的研究中未能在前列腺癌和慢性疲劳综合症的组织样本中检测出XMRV,甚至在早期检出XMRV的样本中也未能检测出XMRV,认为早期的研究结果是实验过程中的污染导致的,排除了XMRV与这两种人类疾病的直接关系。最新研究证实XMRV是在产生前列腺癌细胞系时由两个内源性鼠白血病病毒重组产生的。虽然最近的研究报道XMRV感染与人类疾病之间并没有直接关系,但XMRV仍然是一种未定义的潜在病原体,因为在体外它仍具有感染人类细胞的能力。并且XMRV具有γ逆转录病毒的性质,可以作为模式病毒研究宿主细胞因子与逆转录病毒之间的相互作用。研究发现在宿主细胞中存在一些限制因子APOBEC3和Tetherin蛋白等可以抑制XMRV的复制。 宿主因子MOV10蛋白广泛存在于人类、鼠类等多种物种中,在胚胎干细胞等多种细胞中广泛表达。MOV10蛋白是RNA解旋酶超家族-1中的一个成员,它也是一种RNA诱导的沉默复合体(RISC)的组成部分。近期研究表明MOV10可以抑制包括HIV-1在内的逆转录病毒的复制,具有广谱抗逆转录病毒的性质,在RNA干扰途径中起重要作用。MOV10蛋白本身具有RNA解旋酶的7个保守结构域,在MOV10抑制逆转录病毒中发挥重要作用。 本研究的内容是研究MOV10抑制XMRV复制的作用及其抑制作用机制,探索MOV10抑制活性的关键区域,具有一定的创新性。 本研究采用XMRV前病毒DNA质粒与MOV10质粒/MOV10突变体共转染哺乳动物细胞,产出的病毒再感染细胞,通过检测病毒感染性的方法来验证MOV10对XMRV的抑制作用及其机制以及MOV10对XMRV发挥抑制作用的关键区域。 通过本研究得出以下结论：MOV10具有抑制XMRV复制的活性,过量表达MOV10时,XMRV的感染性显著降低,而降低内源性MOV10的表达时,XMRV的感染性明显增强。MOV10通过包装进XMRV病毒颗粒中,从而在病毒再感染细胞时发挥抑制作用,MOV10发挥抑制作用的主要阶段是XMRV生活周期的逆转录阶段。MOV10发挥抑制作用的关键区域主要是MOV10本身的RNA解旋酶的7个保守结构域,其中结构域Ⅰ、Ⅱ、Ⅲ和Ⅳ的作用非常重要,结构域V和Ⅵ的作用其次,结构域Ia的作用最小。 本研究的成果证明了MOV10可以抑制XMRV的复制,初步阐明了MOV10抑制XMRV复制的机制,明确了MOV10发挥抑制作用的关键结构域。进一步证实了MOV10具有广谱的抗逆转录病毒的活性,在宿主抵抗逆转录病毒感染中发挥了积极重要的作用。
[Abstract]:Heterophil leukemia virus associated virus (XMRV) is a newly discovered 纬-retrovirus with complete replication ability. Early studies have reported that XMRV may be associated with prostate cancer and chronic fatigue syndrome (CFS) in humans, but subsequent studies failed to detect XMRV, in tissue samples of prostate cancer and chronic fatigue syndrome. Even in the early detection of XMRV samples, XMRV, could not detect that the early results of the study were caused by pollution in the experimental process, excluding the direct relationship between XMRV and these two human diseases. New research confirms that XMRV is produced by recombinant two endogenous murine leukemia viruses when prostate cancer cell lines are produced. Although recent studies have reported that there is no direct relationship between XMRV infection and human disease, XMRV is still an undefined potential pathogen because it still has the ability to infect human cells in vitro. Moreover, XMRV has the property of 纬 retrovirus and can be used as a model virus to study the interaction between host cytokines and retroviruses. It was found that some limiting factors, such as APOBEC3 and Tetherin proteins, could inhibit the replication of XMRV in host cells. Host factor MOV10 protein is widely expressed in human, mouse and other species, and is widely expressed in embryonic stem cells and other cells. MOV10 protein is a member of RNA helicase superfamily 1. It is also part of a RNA-induced silencing complex (RISC). Recent studies have shown that MOV10 can inhibit the replication of retroviruses, including HIV-1, and has the properties of broad-spectrum antiretrovirals and plays an important role in the RNA interference pathway. The MOV10 protein itself has seven conserved domains of RNA helicase. It plays an important role in the inhibition of retrovirus by MOV10. The purpose of this study is to study the inhibitory effect of MOV10 on XMRV replication and its mechanism, and to explore the key regions of MOV10 inhibitory activity. In this study, mammalian cells were co-transfected with XMRV precursor virus DNA plasmid and MOV10 plasmid / MOV10 mutants to produce virus reinfection cells. The inhibition of XMRV by MOV10 and its mechanism and the key regions of XMRV inhibition by MOV10 were verified by the method of virus infection. The results showed that MOV10 had the activity of inhibiting XMRV replication. When MOV10 was over-expressed, the infectivity of XMRV was significantly decreased, while that of XMRV was significantly enhanced when the expression of endogenous MOV10 was decreased. MOV10 was packaged into XMRV virus particles. The inhibitory effect of MOV10 is the reverse transcription stage of XMRV life cycle. The key region of inhibition of MOV10 is the seven conserved domains of RNA helicase of MOV10 itself. Domain 鈪，
本文编号：2329648
[Abstract]:Heterophil leukemia virus associated virus (XMRV) is a newly discovered 纬-retrovirus with complete replication ability. Early studies have reported that XMRV may be associated with prostate cancer and chronic fatigue syndrome (CFS) in humans, but subsequent studies failed to detect XMRV, in tissue samples of prostate cancer and chronic fatigue syndrome. Even in the early detection of XMRV samples, XMRV, could not detect that the early results of the study were caused by pollution in the experimental process, excluding the direct relationship between XMRV and these two human diseases. New research confirms that XMRV is produced by recombinant two endogenous murine leukemia viruses when prostate cancer cell lines are produced. Although recent studies have reported that there is no direct relationship between XMRV infection and human disease, XMRV is still an undefined potential pathogen because it still has the ability to infect human cells in vitro. Moreover, XMRV has the property of 纬 retrovirus and can be used as a model virus to study the interaction between host cytokines and retroviruses. It was found that some limiting factors, such as APOBEC3 and Tetherin proteins, could inhibit the replication of XMRV in host cells. Host factor MOV10 protein is widely expressed in human, mouse and other species, and is widely expressed in embryonic stem cells and other cells. MOV10 protein is a member of RNA helicase superfamily 1. It is also part of a RNA-induced silencing complex (RISC). Recent studies have shown that MOV10 can inhibit the replication of retroviruses, including HIV-1, and has the properties of broad-spectrum antiretrovirals and plays an important role in the RNA interference pathway. The MOV10 protein itself has seven conserved domains of RNA helicase. It plays an important role in the inhibition of retrovirus by MOV10. The purpose of this study is to study the inhibitory effect of MOV10 on XMRV replication and its mechanism, and to explore the key regions of MOV10 inhibitory activity. In this study, mammalian cells were co-transfected with XMRV precursor virus DNA plasmid and MOV10 plasmid / MOV10 mutants to produce virus reinfection cells. The inhibition of XMRV by MOV10 and its mechanism and the key regions of XMRV inhibition by MOV10 were verified by the method of virus infection. The results showed that MOV10 had the activity of inhibiting XMRV replication. When MOV10 was over-expressed, the infectivity of XMRV was significantly decreased, while that of XMRV was significantly enhanced when the expression of endogenous MOV10 was decreased. MOV10 was packaged into XMRV virus particles. The inhibitory effect of MOV10 is the reverse transcription stage of XMRV life cycle. The key region of inhibition of MOV10 is the seven conserved domains of RNA helicase of MOV10 itself. Domain 鈪，
本文编号：2329648
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