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A clathrin, caveolae, and dynamin-independent endocytic pathway requiring free membrane cholesterol drives HIV-1 internalization and infection in polarized trophoblastic cells.
J Mol Biol. 2007 May 18; 368(5):1267-83.JM

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.

Authors+Show Affiliations

Research Center in Infectious Diseases, CHUL Research Center, and Department of Medical Biology, Faculty of Medicine, Laval University, Quebec, Canada G1V 4G2.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17395200

Citation

Vidricaire, Gaël, and Michel J. Tremblay. "A Clathrin, Caveolae, and Dynamin-independent Endocytic Pathway Requiring Free Membrane Cholesterol Drives HIV-1 Internalization and Infection in Polarized Trophoblastic Cells." Journal of Molecular Biology, vol. 368, no. 5, 2007, pp. 1267-83.
Vidricaire G, Tremblay MJ. A clathrin, caveolae, and dynamin-independent endocytic pathway requiring free membrane cholesterol drives HIV-1 internalization and infection in polarized trophoblastic cells. J Mol Biol. 2007;368(5):1267-83.
Vidricaire, G., & Tremblay, M. J. (2007). A clathrin, caveolae, and dynamin-independent endocytic pathway requiring free membrane cholesterol drives HIV-1 internalization and infection in polarized trophoblastic cells. Journal of Molecular Biology, 368(5), 1267-83.
Vidricaire G, Tremblay MJ. A Clathrin, Caveolae, and Dynamin-independent Endocytic Pathway Requiring Free Membrane Cholesterol Drives HIV-1 Internalization and Infection in Polarized Trophoblastic Cells. J Mol Biol. 2007 May 18;368(5):1267-83. PubMed PMID: 17395200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A clathrin, caveolae, and dynamin-independent endocytic pathway requiring free membrane cholesterol drives HIV-1 internalization and infection in polarized trophoblastic cells. AU - Vidricaire,Gaël, AU - Tremblay,Michel J, Y1 - 2007/03/12/ PY - 2006/12/21/received PY - 2007/03/02/revised PY - 2007/03/02/accepted PY - 2007/3/31/pubmed PY - 2007/7/18/medline PY - 2007/3/31/entrez SP - 1267 EP - 83 JF - Journal of molecular biology JO - J. Mol. Biol. VL - 368 IS - 5 N2 - 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. SN - 0022-2836 UR - https://www.unboundmedicine.com/medline/citation/17395200/A_clathrin_caveolae_and_dynamin_independent_endocytic_pathway_requiring_free_membrane_cholesterol_drives_HIV_1_internalization_and_infection_in_polarized_trophoblastic_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2836(07)00332-4 DB - PRIME DP - Unbound Medicine ER -