HIV-1 buds and accumulates in "Nonacidic" endosomes of macrophages

HIV-1 buds and accumulates in "Nonacidic" endosomes of macrophages
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DOI:
10.1016/j.chom.2007.06.011
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发表时间:
2007-08-01
影响因子:
30.3
通讯作者:
Benaroch, Philippe
Benaroch, Philippe
中科院分区:
医学1区
文献类型:
--
作者:
Jouve, Mabel;Sol-Foulon, Nathalie;Benaroch, Philippe

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巨噬细胞代表HIV 1感染患者中的病毒储库,并将病毒颗粒积聚在内体区室中,在那里它们长时间保持感染性。为了确定HIV-1如何在变得高度酸性和蛋白水解的内吞隔室中存活,并研究这些含病毒隔室的性质,我们对HIV-1感染的原代巨噬细胞进行了超微结构研究。内体区室含有新形成的病毒粒子,而不是内化的病毒粒子。与相同感染细胞内不含病毒蛋白的内吞区室相反,含有病毒的区室不酸化。酸化的缺乏与不能将质子泵空泡ATP酶募集到病毒组装室中有关。这可能会阻止它与溶酶体融合,因为酸化是内体成熟所必需的。因此,HIV-1已经开发出一种在感染的巨噬细胞内存活的策略,包括防止专门的内吞病毒组装室内的酸化。
Macrophages represent viral reservoirs in HIV1 -infected patients and accumulate viral particles within an endosomal compartment where they remain infectious for long periods of time. To determine how HIV-1 survives in endocytic compartments that become highly acidic and proteolytic and to study the nature of these virus-containing compartments, we carried out an ultrastructural study on HIV-1 -infected primary macrophages. The endosomal compartments contain newly formed virions rather than internalized ones. In contrast to endocytic compartments free of viral proteins within the same infected cells, the virus containing compartments do not acidify. The lack of acidification is associated with an inability to recruit the proton pump vacuolar ATPase into the viral assembly compartment. This may prevent its fusion with lysosomes, since acidification is required for the maturation of endosomes. Thus, HIV-1 has developed a strategy for survival within infected macrophages involving prevention of acidification within a devoted endocytic virus assembly compartment.