The R-U5-5' leader sequence of neurovirulent wild mouse retrovirus contains an element controlling the incubation period of neurodegenerative disease
The R-U5-5' leader sequence of neurovirulent wild mouse retrovirus contains an element controlling the incubation period of neurodegenerative disease
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神经毒力野生小鼠逆转录病毒的R-U5-5前导序列含有控制神经退行性疾病潜伏期的元件
DOI：
10.1128/jvi.65.4.1877-1883.1991
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发表时间：
1991
影响因子：
5.4
通讯作者：
F. McAtee
中科院分区：
文献类型：
--
作者：
J. Portis;S. Perryman;F. McAtee
野生小鼠嗜生态逆转录病毒CasBrE在新生儿接种后引起海绵状神经退行性疾病，潜伏期为2至12个月。我们之前的研究表明，从Friend小鼠白血病病毒（FB29）株中引入长末端重复序列（LTR）和gag-pol序列可导致疾病发作的急剧加速。嵌合病毒FrCasE由含有野生小鼠病毒3' pol和env序列的FB29基因组组成，可诱导高度可预测的致死性神经退行性疾病，潜伏期仅为16天。在这里，我们报告了作为潜伏期长度的主要决定因素的序列位于病毒基因组的5‘端，位于LTR R区域的KpnI位点和pr65gag （R- u5 -5’先导）开始密码子的5'处的PstI位点之间。该区域包含tRNA引物结合位点、亚基因组env mRNA的剪接供体位点和包装序列。计算机辅助序列分析未能在该区域找到DNA增强子一致序列的证据。此外，env 3‘端的ClaI位点与LTR R区的KpnI位点（包括U3）之间的基因组区域内的序列也会影响疾病的潜伏期，但这种影响明显弱于R- u5 -5’先导序列。然而，这种U3效应似乎与直接重复次数无关，因为删除含有核因子结合结构域一致序列的两个42碱基重复序列中的一个对疾病的潜伏期没有影响。根据组织中总病毒DNA的Southern blot分析，这些序列对潜伏期的影响似乎与病毒在中枢神经系统的复制水平有关。所有被分析的嵌合病毒，不论其神经毒性如何，在脾脏中复制到相当水平，并诱导相当水平的病毒血症。
The wild mouse ecotropic retrovirus CasBrE causes a spongiform neurodegenerative disease after neonatal inoculation, with an incubation period ranging from 2 to 12 months. We previously showed that introduction of long terminal repeat (LTR) and gag-pol sequences from a strain of Friend murine leukemia virus (FB29) resulted in a dramatic acceleration of the onset of the disease. The chimeric virus FrCasE, which consisted of the FB29 genome containing 3' pol and env sequences from the wild mouse virus, induced a highly predictable, lethal neurodegenerative disease with an incubation period of only 16 days. Here we report that the sequences which are primary determinants of the length of the incubation period are located in the 5' end of the viral genome between a KpnI site in the R region of the LTR and a PstI site immediately 5' of the start codon for pr65gag (R-U5-5' leader). This region contains the tRNA primer binding site, splice donor site for the subgenomic env mRNA, and the packaging sequence. Computer-assisted sequence analysis failed to find evidence of a consensus sequence for a DNA enhancer in this region. In addition, sequences within a region of the genome between a ClaI site at the 3' end of env to the KpnI site in the R region of the LTR (inclusive of U3) also influenced the incubation period of the disease, but the effect was distinctly weaker than that of the R-U5-5' leader sequence. This U3 effect, however, appeared to be independent of the number of direct repeats, since deletion of one of two duplicated 42-base repeats containing consensus sequences of nuclear-factor binding domains had no effect on the incubation period of the disease. On the basis of Southern blot analysis of total viral DNA in the tissues, the effect of these sequences on the incubation period appeared to be related to the level of virus replication in the central nervous system. All of the chimeric viruses analyzed, irrespective of neurovirulence, replicated to comparable levels in the spleen and induced comparable levels of viremia.
增强子序列不稳定性使鼠白血病病毒表达的细胞库多样化。
影响因子：
3.7
作者：
Spiro,C;Li,JP;Bestwick,RK;Kabat,D
通讯作者：
Kabat,D
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