Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2005-11-7
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6517-30
pubmed:dateRevised
2010-10-11
pubmed:meshHeading
pubmed-meshheading:16272306-ADP-Ribosylation Factors, pubmed-meshheading:16272306-Androstadienes, pubmed-meshheading:16272306-Base Sequence, pubmed-meshheading:16272306-Cell Line, pubmed-meshheading:16272306-Cell Polarity, pubmed-meshheading:16272306-DNA, Viral, pubmed-meshheading:16272306-Endocytosis, pubmed-meshheading:16272306-Endosomes, pubmed-meshheading:16272306-Female, pubmed-meshheading:16272306-HIV Core Protein p24, pubmed-meshheading:16272306-HIV Infections, pubmed-meshheading:16272306-HIV-1, pubmed-meshheading:16272306-Humans, pubmed-meshheading:16272306-Placenta, pubmed-meshheading:16272306-Pregnancy, pubmed-meshheading:16272306-T-Lymphocytes, pubmed-meshheading:16272306-Trophoblasts, pubmed-meshheading:16272306-rab GTP-Binding Proteins, pubmed-meshheading:16272306-rab5 GTP-Binding Proteins
pubmed:year
2005
pubmed:articleTitle
Rab5 and Rab7, but not ARF6, govern the early events of HIV-1 infection in polarized human placental cells.
pubmed:affiliation
Research Center in Infectious Diseases, Centre Hospitalier de l'Université Laval Research Center, and Faculty of Medicine, Laval University, Quebec City, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't