Construction and infection of a new simian/human immunodeficiency chimeric virus (SHIV) containing the integrase gene of the human immunodeficiency virus type 1 genome and analysis of its adaptation to monkey cells
Construction and infection of a new simian/human immunodeficiency chimeric virus (SHIV) containing the integrase gene of the human immunodeficiency virus type 1 genome and analysis of its adaptation to monkey cells
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DOI：
10.1016/j.micinf.2008.02.001
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发表时间：
2008-04-01
影响因子：
5.8
通讯作者：
Ido, Eiji
中科院分区：
文献类型：
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作者：
Akiyama, Hisashi;Ishimatsu, Misa;Ido, Eiji
扩展SHIV-1基因组中的HIV-1衍生区域可能有助于阐明决定宿主范围的病毒限制因子。在本研究中，我们构建了一种新的SHIV，除了HIV-1的3'半基因组区域外，还具有HIV-1的逆转录酶和整合酶编码区域。这种SHIV，称为SHIVrti/3rn，可以在猴CD 4（+）T细胞系HSC-F中复制，尽管它在猴PBMC中的复制非常弱。SHIVrti/3rn在HSC-F细胞中传代26周后，逐渐开始在猴PBMC中复制。这种适应猴细胞的病毒，称为SHIVrti/3rti，可以在恒河猴中复制。对SHIVrti/3rn的全基因组进行测序，发现其与SHIVrti/3rn在11个位置上不同。我们构建了一系列具有这些突变中的部分或全部的突变体，并研究了它们的复制动力学。突变分析表明，所有的突变，但主要是在env中的突变，负责在HSC-F细胞中的适应，并足以在恒河猴PBMC中复制。在迄今为止报道的所有可以在体内感染恒河猴的SHIV中，SHIVrti/3rti是遗传上最接近HIV-1的一种。(C)2008年，Elsevier Masson SAS。All rights reserved.
Expanding the HIV-1-derived regions in the SHIV genome may help to clarify the viral restriction factors determining the host range. In this study, we constructed a new SHIV having the reverse transcriptase and integrase-encoding regions of HIV-1 in addition to the 3' half genomic region of HIV-1. This SHIV, termed SHIVrti/3rn, could replicate in a monkey CD4(+)T cell line, HSC-F, although its replication in monkey PBMCs was very weak. After SHIVrti/3rn was passaged in HSC-F cells for 26 weeks, it gradually began to replicate in monkey PBMCs. This monkey-cell-adapted virus, termed SHIVrti/3rnP, could replicate in rhesus macaques. The whole genome of SHIVrti/3rnP was sequenced and was found to differ from SHIVrti/3rn at eleven positions. We constructed a series of mutants having some or all of these mutations and investigated their replication kinetics. The mutational analysis revealed that all of the mutations, but mainly the mutations in env, were responsible for the adaptation in HSC-F cells and were enough to replicate in rhesus PBMCs. Of all the SHIVs reported so far that can infect rhesus monkeys in vivo, SHIVrti/3rnP is the one that is genetically the closest to HIV-1. (C) 2008 Elsevier Masson SAS. All rights reserved.