CXCR4- and CCR5-Tropic HIV-1 Clones Are Both Tractable to Grow in Rhesus Macaques.
CXCR4- and CCR5-Tropic HIV-1 Clones Are Both Tractable to Grow in Rhesus Macaques.
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DOI：
10.3389/fmicb.2018.02510
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发表时间：
2018
影响因子：
5.2
通讯作者：
Nomaguchi M
中科院分区：
文献类型：
--
作者：
Doi N;Miura T;Mori H;Sakawaki H;Koma T;Adachi A;Nomaguchi M
目前HIV-1研究的一个主要问题是建立模型系统，以反映或模拟在感染人类中实际观察到的病毒复制和发病机制。为此，利用猕猴作为感染目标的各种策略一直被追求。特别是，艾滋病毒-1衍生物对恒河猴的实验性感染被认为在可行的情况下最适合研究艾滋病毒-1与人类在各种情况下的相互作用。最近，通过体外遗传操作和病毒细胞适应，我们成功地产生了一系列具有CXCR4和CCR5嗜性的HIV-1衍生物，它们在猕猴细胞中不同程度地生长。在这些病毒中，那些具有最佳复制潜力的病毒可以通过对抗主要限制因子TRIM5、APOBEC3和Tetherin蛋白在猕猴细胞中与致病SIVmac相似地生长。本研究用嗜CXCR4(MN4/LSDQgtu)或嗜CCR5(GTU+A4CI1)病毒攻击恒河猴。这两种病毒被发现能有效地感染恒河猴，它们是恒河猴嗜性HIV-1(HIV-1rmt)。然而，在感染后5-6周及以后，感染猕猴的血浆病毒RNA水平降至检测不到的水平。虽然MN4/LSDQgtu在恒河猴外周血单核细胞中复制良好，但在动物体内的生长情况比GTU+A4CI1好得多。据我们所知，这是第一份证明HIV-1衍生物(变种)在恒河猴体内生长的报告。这些病毒当然构成了产生对恒河猴致病的HIV-1rmt克隆的坚实基础，尽管它们比迄今报道的致病SIVmac和Shiv克隆生长得更差。
A major issue for present HIV-1 research is to establish model systems that reflect or mimic viral replication and pathogenesis actually observed in infected humans. To this end, various strategies using macaques as infection targets have long been pursued. In particular, experimental infections of rhesus macaques by HIV-1 derivatives have been believed to be best suited, if practicable, for studies on interaction of HIV-1 and humans under various circumstances. Recently, through in vitro genetic manipulations and viral cell-adaptations, we have successfully generated a series of HIV-1 derivatives with CXCR4-tropism or CCR5-tropism that grow in macaque cells to various degrees. Of these viruses, those with best replicative potentials can grow comparably with a pathogenic SIVmac in macaque cells by counteracting major restriction factors TRIM5, APOBEC3, and tetherin proteins. In this study, rhesus macaques were challenged with CXCR4-tropic (MN4/LSDQgtu) or CCR5-tropic (gtu + A4CI1) virus. The two viruses were found to productively infect rhesus macaques, being rhesus macaque-tropic HIV-1 (HIV-1rmt). However, plasma viral RNA was reduced to be an undetectable level in infected macaques at 5–6 weeks post-infection and thereafter. While replicated similarly well in rhesus peripheral blood mononuclear cells, MN4/LSDQgtu grew much better than gtu + A4CI1 in the animals. To the best of our knowledge, this is the first report demonstrating that HIV-1 derivatives (variants) grow in rhesus macaques. These viruses certainly constitute firm bases for generating HIV-1rmt clones pathogenic for rhesus monkeys, albeit they grow more poorly than pathogenic SIVmac and SHIV clones reported to date.
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影响因子：
10.5
作者：
Dahabieh MS;Battivelli E;Verdin E
通讯作者：
Verdin E
DOI：
10.1038/nrmicro3503
发表时间：
2015-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Campbell EM;Hope TJ
通讯作者：
Hope TJ
影响因子：
32.4
作者：
Blanco-Melo D;Venkatesh S;Bieniasz PD
通讯作者：
Bieniasz PD
猕猴细胞中CCR5-Tropic/CXCR4-纤维化HIV-1MT克隆的生长潜力。
影响因子：
5.2
作者：
Doi N;Okubo A;Yamane M;Sakai Y;Adachi A;Nomaguchi M
通讯作者：
Nomaguchi M
DOI：
10.1006/bbrc.1999.1364
发表时间：
1999-09-24
影响因子：
3.1
作者：
Akari, H;Fukumori, T;Adachi, A
通讯作者：
Adachi, A