Neurodegenerative disease induced by the wild mouse ecotropic retrovirus is markedly accelerated by long terminal repeat and gag-pol sequences from nondefective Friend murine leukemia virus
Neurodegenerative disease induced by the wild mouse ecotropic retrovirus is markedly accelerated by long terminal repeat and gag-pol sequences from nondefective Friend murine leukemia virus
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来自无缺陷弗兰德鼠白血病病毒的长末端重复序列和 gag-pol 序列显着加速了野生小鼠亲嗜性逆转录病毒引起的神经退行性疾病
DOI：
10.1128/jvi.64.4.1648-1656.1990
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发表时间：
1990
影响因子：
5.4
通讯作者：
C. Garon
中科院分区：
文献类型：
--
作者：
J. Portis;S. Czub;C. Garon
野生小鼠嗜亲性逆转录病毒（WM-E）在2个月至长达1年的可变潜伏期后在小鼠中诱导海绵状神经变性疾病。我们分离出一个WM-E（15-1）的分子克隆，它具有弱神经毒性（发病率8%），但具有高度致白血病性（发病率45%）。观察到淋巴细胞和粒细胞白血病，这些白血病往往是神经浸润性的。构建了含有来自Friend鼠白血病病毒（FB 29）克隆的15-1的env和3' pol序列以及长末端重复（LTR）、gag和5' pol序列的嵌合病毒。FB 29先前已被证明在中枢神经系统（CNS）中复制到高水平，但本身不是神经毒性的。这一发现在目前的研究中在DNA水平得到了证实。令人惊讶的是，用嵌合病毒（FrCasE）腹膜内接种新生IRW小鼠导致加速的神经退行性疾病，潜伏期仅为16天，并且在接种后23天一致致命。将15-1的LTR引入FrCasE基因组产生了具有介于15-1和FrCasE的神经毒力之间的神经毒力程度的病毒（FrCasEL）。在用15-1、FrCasE或FrCasEL接种的小鼠的脾脏中，没有发现病毒血症水平或病毒DNA的相对水平的差异。然而，CNS中病毒DNA的水平与各病毒的神经毒力的相对程度相关（FrCasE大于FrCasEL大于15-1）。因此，WM-E（15-1）的env和3' pol序列是神经毒力所必需的，但是FB 29的LTR和gag-pol区域内的元件对CNS感染水平和神经变性的发展速率具有深远的影响。
The wild mouse ecotropic retrovirus (WM-E) induces a spongiform neurodegenerative disease in mice after a variable incubation period of 2 months to as long as 1 year. We isolated a molecular clone of WM-E (15-1) which was weakly neurovirulent (incidence, 8%) but was highly leukemogenic (incidence, 45%). Both lymphoid and granulocytic leukemias were observed, and these leukemias were often neuroinvasive. A chimeric virus was constructed containing the env and 3' pol sequences of 15-1 and long terminal repeat (LTR), gag, and 5' pol sequences from a clone of Friend murine leukemia virus (FB29). FB29 has been shown previously to replicate to high levels in the central nervous system (CNS) but is not itself neurovirulent. This finding was confirmed at the DNA level in the current study. Surprisingly, intraperitoneal inoculation of neonatal IRW mice with the chimeric virus (FrCasE) caused an accelerated neurodegenerative disease with an incubation period of only 16 days and was uniformly fatal by 23 days postinoculation. Introduction of the LTR of 15-1 into the FrCasE genome yielded a virus (FrCasEL) with a degree of neurovirulence intermediate between those of 15-1 and FrCasE. No differences were found in the levels of viremia or the relative levels of viral DNA in the spleens of mice inoculated with 15-1, FrCasE, or FrCasEL. However, the levels of viral DNA in the CNS correlated with the relative degrees of neurovirulence of the respective viruses (FrCasE greater than FrCasEL greater than 15-1). Thus, the env and 3' pol sequences of WM-E (15-1) were required for neurovirulence, but elements within the LTR and gag-pol regions of FB29 had a profound influence on the level of CNS infection and the rate of development of neurodegeneration.
逆转录病毒和小鼠胚胎：神经毒力和经胎盘抗病毒治疗的快速模型。
DOI：
10.1126/science.3037694
发表时间：
1987
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Sharpe,AH;Jaenisch,R;Ruprecht,RM
通讯作者：
Ruprecht,RM