Construction of a novel SHIV having an HIV-1-derived protease gene and its infection to rhesus macaques: a useful tool for in vivo efficacy tests of protease inhibitors
Construction of a novel SHIV having an HIV-1-derived protease gene and its infection to rhesus macaques: a useful tool for in vivo efficacy tests of protease inhibitors
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DOI：
10.1016/j.micinf.2007.01.005
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发表时间：
2007-04-01
影响因子：
5.8
通讯作者：
Ido, Eiji
中科院分区：
文献类型：
--
作者：
Ishimatsu, Misa;Suzuki, Hajime;Ido, Eiji
我们生成了一种新型 SHIV（称为 SHIV-pr），它在 SIVmac 基因组的相应位置拥有 HIV-1 衍生蛋白酶（PR）基因。 SHIV-pr 在人和猴 CD4(+) T 淋巴细胞系以及恒河猴 PBMC 中具有复制能力。在组织培养水平上存在肽类似物 PR 抑制剂的情况下，SHIV-pr 的病毒生长被完全阻断。当将 SHIV-pr 静脉注射到两只恒河猴中时，其中一只猴子出现了微弱但持久的持续感染，而另一只猴子的感染只是暂时的。为了通过适应来增强病毒的生长能力，我们将病毒从猴子体内传代到第四代。血浆病毒载量的初始峰值以及设定值逐代增加，并达到亲本病毒 SIVmac 的水平。当给三只感染SHIV-pr的猴子口服含有克力芝胶囊（两种PR抑制剂洛匹那韦和利托那韦的混合物）的药物4周后，血浆病毒载量下降到接近或低于检测限，并在停止用药后迅速反弹。结果表明，SHIV-pr 可用于利用猴子评估 PR 抑制剂。 (c) 2007 年 Elsevier Masson SAS。版权所有。
We generated a novel SHIV (termed SHIV-pr) that possesses the HIV-1-derived protease (PR) gene in the corresponding position in the SIVmac genome. SHIV-pr is replication-competent in human and monkey CD4(+) T lymphoid cell lines as well as rhesus macaque PBMCs. The viral growth of SHIV-pr was completely blocked in the presence of a peptide-analog PR inhibitor at the tissue culture level. When SHIV-pr was intravenously inoculated into two rhesus macaques, it resulted in a weak but long-lasting persistent infection in one monkey, whereas the infection of another was only temporary. To enhance the viral growth competence by adaptation, we then passaged the virus in vivo from a monkey up to the fourth generation. The initial peak values of plasma viral loads as well as the setpoint values increased generation by generation and reached those of a parental virus SIVmac. When a medication using the content of Kaletra capsule (a mixture of two PR inhibitors, lopinavir and ritonavir) was orally given to three SHIV-pr-infected monkeys for 4 weeks, plasma viral loads dropped to near or below the detection limit and quickly rebounded after the cessation of medication. The results suggest that SHIV-pr can be used to evaluate PR inhibitors using monkeys. (c) 2007 Elsevier Masson SAS. All rights reserved.