Human Ubc9 is involved in intracellular HIV-1 Env stability after trafficking out of the trans-Golgi network in a Gag dependent manner.
Human Ubc9 is involved in intracellular HIV-1 Env stability after trafficking out of the trans-Golgi network in a Gag dependent manner.
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DOI：
10.1371/journal.pone.0069359
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wood C
中科院分区：
文献类型：
--
作者：
Bohl CR;Abrahamyan LG;Wood C
细胞 E2 Sumo 缀合酶 Ubc9 与 HIV-1 Gag 相互作用，对于感染性 HIV-1 病毒颗粒的组装非常重要。在之前的研究中，我们证明，在缺乏 Ubc9 的情况下，病毒粒子组装的缺陷与成熟细胞内包膜 (Env) 水平的降低有关，从而影响 Env 掺入病毒粒子和病毒粒子的感染性。我们进一步表征了 Ubc9 敲低对 HIV 包膜加工和组装的影响。我们发现gp160在内质网（ER）中的稳定性及其向跨高尔基体网络（TGN）的运输不受影响，这表明Ubc9耗尽的细胞中细胞内成熟Env水平降低是由于成熟Env gp120在从gp160裂解并运输出TGN后选择性降解所致。人们发现 Gag 和成熟 Env 水平的降低与质膜和脂筏有关，这表明这些病毒蛋白没有正确运输到组装位点。当用溶酶体抑制剂联合治疗时，细胞内 gp120 得到部分挽救。综上所述，我们的结果表明，在缺乏 Ubc9 的情况下，gp120 可能会优先在溶酶体中降解，然后再运输到装配位点，从而导致有缺陷的病毒颗粒的产生。这项研究为将 HIV-1 gp120 加工和包装成成熟 HIV-1 病毒体提供了进一步的见解。
The cellular E2 Sumo conjugase, Ubc9 interacts with HIV-1 Gag, and is important for the assembly of infectious HIV-1 virions. In the previous study we demonstrated that in the absence of Ubc9, a defect in virion assembly was associated with decreased levels of mature intracellular Envelope (Env) that affected Env incorporation into virions and virion infectivity. We have further characterized the effect of Ubc9 knockdown on HIV Env processing and assembly. We found that gp160 stability in the endoplasmic reticulum (ER) and its trafficking to the trans-Golgi network (TGN) were unaffected, indicating that the decreased intracellular mature Env levels in Ubc9-depleted cells were due to a selective degradation of mature Env gp120 after cleavage from gp160 and trafficked out of the TGN. Decreased levels of Gag and mature Env were found to be associated with the plasma membrane and lipid rafts, which suggest that these viral proteins were not trafficked correctly to the assembly site. Intracellular gp120 were partially rescued when treated with a combination of lysosome inhibitors. Taken together our results suggest that in the absence of Ubc9, gp120 is preferentially degraded in the lysosomes likely before trafficking to assembly sites leading to the production of defective virions. This study provides further insight in the processing and packaging of the HIV-1 gp120 into mature HIV-1 virions.
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影响因子：
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作者：
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影响因子：
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DOI：
10.1073/pnas.0909176106
发表时间：
2009-12-15
影响因子：
11.1
作者：
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通讯作者：
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