HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vidricaire, G. Articles by Tremblay, M. J. Search for Related Content PubMed PubMed Citation Articles by Vidricaire, G. Articles by Tremblay, M. J.

Rab5 and Rab7, but Not ARF6, Govern the Early Events of HIV-1 Infection in Polarized Human Placental Cells¹

Research Center in Infectious Diseases, Centre Hospitalier de l’Université Laval Research Center, and Faculty of Medicine, Laval University, Quebec City, Quebec, Canada

Trophoblasts, the structural cells of the placenta, are thought to play a determinant role in in utero HIV type 1 (HIV-1) transmission. We have accumulated evidence suggesting that HIV-1 infection of these cells is associated with uptake by an unusual clathrin/caveolae-independent endocytic pathway and that endocytosis is followed by trafficking through multiple organelles. Furthermore, part of this trafficking involves the transit of HIV-1 from transferrin-negative to EEA1 and transferrin-positive endosomes, suggesting a merger from nonclassical to classical endocytic pathways in these cells. In the present article, the relationship between the presence of HIV-1 within specific endosomes and infection was studied. We demonstrate that viral infection is virtually lost when endosome inhibitors are added shortly after exposure to HIV-1. Thus, contrary to what is seen in CD4⁺ T lymphocytes, the initial presence of HIV-1 within the endosomes is mandatory for infection to take place. Importantly, this process is independent of the viral envelope proteins gp120 and gp41. The Rab family of small GTPases coordinates the vesicular transport between the different endocytic organelles. Experiments performed with various expression vectors indicated that HIV-1 infection in polarized trophoblasts relies on Rab5 and Rab7 without the contribution of Arf6 or Rab11. Furthermore, we conclude that Rab5 drives movements from raft-rich region to early endosomes, and this transit is required for subsequently reaching late endosomes via Rab7. This complex trafficking is mandatory for HIV-1 infection to proceed in human polarized trophoblasts.

This article has been cited by other articles:

				H. L. Johns, S. Berryman, P. Monaghan, G. J. Belsham, and T. Jackson A Dominant-Negative Mutant of rab5 Inhibits Infection of Cells by Foot-and-Mouth Disease Virus: Implications for Virus Entry J. Virol., June 15, 2009; 83(12): 6247 - 6256. [Abstract] [Full Text] [PDF]

				E. H. Sklan, K. Staschke, T. M. Oakes, M. Elazar, M. Winters, B. Aroeti, T. Danieli, and J. S. Glenn A Rab-GAP TBC Domain Protein Binds Hepatitis C Virus NS5A and Mediates Viral Replication J. Virol., October 15, 2007; 81(20): 11096 - 11105. [Abstract] [Full Text] [PDF]

				P. Bhat and D. A. Anderson Hepatitis B Virus Translocates across a Trophoblastic Barrier J. Virol., July 1, 2007; 81(13): 7200 - 7207. [Abstract] [Full Text] [PDF]