当前位置： SCI文献检索 > JOURNAL OF MOLECULAR BIOLOGY期刊下所有文献 > A clathrin, caveolae, and dynamin-independent endocytic pathway requiring free membrane cholesterol drives HIV-1 internalization and infection in polarized trophoblastic cells.

A clathrin, caveolae, and dynamin-independent endocytic pathway requiring free membrane cholesterol drives HIV-1 internalization and infection in polarized trophoblastic cells.

Abstract：

: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-beta-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.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Vidricaire G,Tremblay MJ

doi

10.1016/j.jmb.2007.03.003

subject

Has Abstract

pub_date

2007-05-18 00:00:00

pages

1267-83

issue

5

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(07)00332-4

journal_volume

368

pub_type

杂志文章

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