کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2188477 1096171 2007 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A Clathrin, Caveolae, and Dynamin-independent Endocytic Pathway Requiring Free Membrane Cholesterol Drives HIV-1 Internalization and Infection in Polarized Trophoblastic Cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
A Clathrin, Caveolae, and Dynamin-independent Endocytic Pathway Requiring Free Membrane Cholesterol Drives HIV-1 Internalization and Infection in Polarized Trophoblastic Cells
چکیده انگلیسی

In human trophoblastic cells, a correlation between early endosomal trafficking of HIV-1 and virus infection was previously documented. However, if HIV-1 is massively internalized in these cells, the endocytic pathway(s) responsible for viral uptake is still undefined. Here we address this vital question. Amongst all the putative endocytic pathways present in polarized trophoblastic cells, we demonstrate that HIV-1 infection of these cells is independent of clathrin-mediated endocytosis and macropinocytosis. Importantly, treatment with the cholesterol-sequestering drug filipin severely impairs virus internalization, whereas the cholesterol-depleting compound methyl-β-cyclodextrin has no impact on this pathway. Moreover, viral internalization is unaffected by overexpression of a mutant dynamin 2 or treatment with a kinase or tyrosine phosphatase inhibitor. Thus, HIV-1 infection in polarized trophoblastic cells occurs primarily via a clathrin, caveolae, and dynamin-independent pathway requiring free cholesterol. Notably, even though HIV-1 did not initially co-localize with transferrin, some virions migrate at later time points to transferrin-enriched endosomes, suggesting an unusual transit from the non-classical pathway to early endosomes. Finally, virus internalization in these cells does not involve the participation of microtubules but relies partly on actin filaments. Collectively these findings provide unprecedented information on the route of HIV-1 internalization in polarized human trophoblasts.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 368, Issue 5, 18 May 2007, Pages 1267–1283
نویسندگان
, ,