A molecular clone of simian-human immunodeficiency virus (ΔvpuSHIVKU-1bMC33) with a truncated, non-membrane-bound vpu results in rapid CD4+ T cell loss and neuro-AIDS in pig-tailed macaques
A molecular clone of simian-human immunodeficiency virus (ΔvpuSHIVKU-1bMC33) with a truncated, non-membrane-bound vpu results in rapid CD4+ T cell loss and neuro-AIDS in pig-tailed macaques
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DOI：
10.1006/viro.2000.0333
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发表时间：
2000-06-20
期刊：
影响因子：
3.7
通讯作者：
Stephens, EB
中科院分区：
文献类型：
--
作者：
McCormick-Davis, C;Dalton, SB;Stephens, EB
我们报告的作用vpu的分子克隆的猴-人免疫缺陷病毒（SHIVKU-1bMC 33），其中的lat，rev，vpu，env和nef基因来自未克隆的SHIVKU-1b病毒插入到亲本非致病性SHIV-4的遗传背景的发病机制。构建了Vpu的82个氨基酸中有42个氨基酸缺失的突变体（Δ VpuSHIV（KU-1bMC 33））。相分配研究表明，截短的Vpu不是一个完整的膜蛋白，脉冲追踪培养研究表明，接种Delta VpuSHIV（KU-1bMC 33）的细胞释放病毒p27到培养基中，与接种SHIVKU-1bMC 33的培养物相比，动力学略有降低。将Delta VpuSHIV（KU-1bMC 33）接种到两只猪尾猕猴中，导致一只猕猴的CD 4（+）T细胞严重下降和神经系统疾病，另一只猕猴的CD 4（+）T细胞下降较温和。这些结果表明，膜结合的Vpu是不需要的CD 4（+）T细胞的损失和神经系统疾病在SHIV接种的猪尾猕猴。此外，由于达特和Rev中的氨基酸取代与先前报道的非致病性SHIVPPc中的氨基酸取代相同，我们的结果表明，Env和/或Nef中的氨基酸取代是接种该分子克隆后观察到的CD 4 + T细胞损失和神经系统疾病的原因。(C)北京大学出版社.
We report on the role of vpu in the pathogenesis of a molecularly cloned simian-human immunodeficiency virus (SHIVKU-1bMC33), in which the lat, rev, vpu, env, and nef genes derived from the uncloned SHIVKU-1b virus were inserted into the genetic background of parental nonpathogenic SHIV-4. A mutant was constructed (Delta vpuSHIV(KU-1bMC33)) in which 42 of 82 amino acids of Vpu were deleted. Phase partitioning studies revealed that the truncated Vpu was not an integral membrane protein, and pulse-chase culture studies revealed that cells inoculated with Delta vpuSHIV(KU-1bMC33) released viral p27 into the culture medium with slightly reduced kinetics compared with cultures inoculated with SHIVKU-1bMC33. Inoculation of Delta vpuSHIV(KU-1bMC33) into two pig-tailed macaques resulted in a severe decline of CD4(+) T cells and neurological disease in one macaque and a more moderate decline of CD4(+) T cells in the other macaque. These results indicate that a membrane-bound Vpu is not required for the CD4(+) T cell loss and neurological disease in SHIV-inoculated pig-tailed macaques. Furthermore, because the amino acid substitutions in the Tat and Rev were identical to those previously reported for the nonpathogenic SHIVPPc, our results indicate that amino acid substitutions in the Env and/or Nef were responsible for the observed CD4+ T cell loss and neurological disease after inoculation with this molecular clone. (C) 2000 Academic Press.