Skip to main content

Advertisement

HIV-1 internalization in polarized human trophoblasts occurs through a peculiar endocytic pathway

Article metrics

  • 1801 Accesses

  • 2 Citations

Background

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.

Materials and methods

The process through which HIV-1 is endocytosed was studied using different reagents (e.g. chlorpromazine, cholera toxin B, water-soluble cholesterol, colchicine, cytochalasin B, filipin, jasplakinolide, methyl-beta-cyclodextrin, paclitaxel, and vinblastine) and experimental strategies (e.g. transfection of JAR cells with various expression vectors, virus internalization test, infection assay, confocal laser scanning, co-localization analysis and digital image preparation).

Results

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.

Conclusions

We demonstrate that HIV-1 internalization in polarized human trophoblastic cells occurs primarily via a clathrin-, caveolea-, and dynamin-independent pathway which is sensitive to a cholesterol-sequestering drug.

Author information

Correspondence to Michel J Tremblay.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Tremblay, M.J., Vidricaire, G. HIV-1 internalization in polarized human trophoblasts occurs through a peculiar endocytic pathway. Retrovirology 5, O5 (2008) doi:10.1186/1742-4690-5-S1-O5

Download citation

Keywords

  • Paclitaxel
  • Colchicine
  • Cholera
  • Trophoblastic Cell
  • Early Endosome