SEQUENCE-ANALYSIS AND ACUTE PATHOGENICITY OF MOLECULARLY CLONED SIVSMM-PBJ14
SEQUENCE-ANALYSIS AND ACUTE PATHOGENICITY OF MOLECULARLY CLONED SIVSMM-PBJ14
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DOI：
10.1038/345636a0
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发表时间：
1990-06-14
期刊：
影响因子：
64.8
通讯作者：
FULTZ, PN
中科院分区：
文献类型：
--
作者：
DEWHURST, S;EMBRETSON, JE;FULTZ, PN
来自乌白眉猴的猿猴免疫缺陷病毒 PBJ14 分离株 (SIVSMM-PBj14) 是迄今为止描述的致病性最强的灵长类慢病毒，总是在接种后 8 天内引起猪尾猕猴 (Macaco nemestrina) 致命疾病1。作为鉴定影响致病性的病毒基因和基因产物的第一步，SIVSMM-PBjl4 基因组通过聚合酶链式反应扩增为分别为 5.1 和 5.8 KB 的 5' 和 3' 基因组半部，并进行分子克隆。 DNA 序列分析显示，与其他 SIV 具有高度保守性，但病毒长末端重复序列增强子区域存在 22 个碱基对重复，其中包括转录因子 NF-κB 的第二个结合位点。在检查的六个基因组一半中，有四个促成了传染性病毒的形成，这种病毒最早在接种后 6 天就引起了猪尾猕猴的急性疾病和死亡，其病理学、疾病综合征和动力学与非克隆分离株引起的病理学、疾病综合征和动力学没有区别。据我们所知，这是由分子定义的慢病毒引起的急性免疫缺陷病的第一个例子。此外，分子克隆的SIVSMM-PBjl4病毒与非克隆病毒对白眉猴CD4+细胞具有共同的细胞病变性，这一特性可能与其观察到的体内致病性相关。
THE PBJ14 isolate of simian immunodeficiency virus from sooty mangabey monkeys (SIVSMM-PBj14) is the most acutely pathogenic primate lentivirus so far described, always causing fatal disease in pig-tailed macaques(Macaco nemestrina)within 8 days of inoculation1. As a first step in identifying viral genes and gene products that influence pathogenicity, the SIVSMM-PBjl4genome was amplified by the polymerase chain reaction as 5´ and 3´ genomic halves of 5.1 and 5.8 kilobases, respectively, and molecularly cloned. DNA sequence analysis revealed a high degree of conservation with other SIVs, except for a 22-base-pair duplication in the enhancer region of the viral long terminal repeat which included a second binding site for the transcription factor NF-κB. Of six genomic halves examined, four contributed to the formation of infectious virus that induced acute disease and death in pig-tailed macaques as early as 6 days post-inoculation, with pathology, disease syndromes and kinetics indistinguishable from those induced by the uncloned isolate. To our knowledge this is the first example of acute immunodeficiency disease induced by a molecularly defined lentivirus. Furthermore, the molecularly cloned SIVSMM-PBjl4viruses share with the uncloned virus cytopathicity for mangabey CD4+cells, a property that may correlate with their observed pathogenicityin vivo.