Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Virology. 2014 Jul;460-461:1-10. doi: 10.1016/j.virol.2014.04.037. Epub 2014 May 27.
Several derivatives of human immunodeficiency virus type 1 (HIV-1) that evade macaque restriction factors and establish infection in pig-tailed macaques (PtMs) have been described. These monkey-tropic HIV-1s utilize CXCR4 as a co-receptor that differs from CCR5 used by most currently circulating HIV-1 strains. We generated a new monkey-tropic HIV-1 carrying env from a CCR5-tropic subtype C HIV-1 clinical isolate. Using intracellular homologous recombination, we generated an uncloned chimeric virus consisting of at least seven types of recombination breakpoints in the region between vpr and env. The virus increased its replication capacity while maintaining CCR5 tropism after in vitro passage in PtM primary lymphocytes. PtM infection with the adapted virus exhibited high peak viremia levels in plasma while the virus was undetectable at 12-16 weeks. This virus serves as starting point for generating a pathogenic monkey-tropic HIV-1 with CCR5-tropic subtype C env, perhaps through serial passage in macaques.
已经描述了几种逃避猕猴限制因子并在猪尾猕猴（PtM）中建立感染的人类免疫缺陷病毒 1 型（HIV-1）衍生物。这些猴艾滋病毒-1 利用 CXCR4 作为辅助受体，与大多数目前流行的 HIV-1 株使用的 CCR5 不同。我们从 CCR5 嗜性 C 型 HIV-1 临床分离株中产生了一种新的携带 env 的猴艾滋病毒-1。通过细胞内同源重组，我们生成了一种未经克隆的嵌合病毒，该病毒在 vpr 和 env 之间的区域至少有七种类型的重组断点。该病毒在体外传代于 PtM 原代淋巴细胞后，在保持 CCR5 嗜性的同时增加了复制能力。适应病毒的 PtM 感染导致血浆中出现高峰值病毒血症水平，而在 12-16 周时病毒无法检测到。该病毒为生成具有 CCR5 嗜性 C 型 env 的致病性猴艾滋病毒-1提供了起点，可能是通过在猕猴中连续传代。
