Fusion of HIV-1 envelope-expressing cells to human glomerular endothelial cells through an CXCR4-mediated mechanism View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-10

AUTHORS

Patricio E. Ray, Ángel A. Soler-García, Lian Xu, Carl Soderland, Robert Blumenthal, Anu Puri

ABSTRACT

A central question in the pathogenesis of HIV-associated thrombotic microangiopathic (HIV-TMA) lesions is whether the HIV-1 envelope glycoprotein (HIV-1 Env) can interact directly with human glomerular endothelial cells (HGECs) through specific HIV-1 co-receptors. The goal of this study was to determine whether cultured primary HGECs express significant levels of the major HIV-1 co-receptors CD4, CXCR4, and/or CCR5 to allow fusion interactions with HIV-1. The expression of CD4, CXCR-4 and CCR-5 was assessed in cultured HGECs by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry using specific antibodies. The HIV-1 Env-mediated membrane fusion of target glomerular cells was evaluated by a fluorescent dye transfer-based cell-cell fusion microscopic method. HGECs express CXCR4 mRNA and protein as determined by RT-PCR and immunostaining with phycoerythrin-conjugated anti-CXCR4 Mab 12G5. CD4 and CCR5 were not detected in HGECs, either by RT-PCR or by surface immunostaining with specific antibodies. Incubation of HGECs with cells expressing a CD4-independent envelope strain (HIV-1IIIB-8x) and the CD4-dependent envelope strain (HIV-1IIIB) resulted in transfer of fluorescent dyes of approximately 20% after 8-16 h incubation at 37 degrees C. Incubation in the presence of inhibitors (C34, which blocks six-helix bundle formation, and AMD3100, which interacts with CXCR4) reduced dye transfer by 60%-80%, confirming that the dye transfer was specific with respect to gp120-gp41-mediated fusion. Cultured primary HGECs express CXCR4 but not CD4 or CCR5. The ability of HGECs to promote fusion by a CD4-independent HIV-1 envelope glycoprotein suggests that these cells may become a potential direct target of certain HIV-1 isolates. More... »

PAGES

1401-1409

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00467-005-1950-5

DOI

http://dx.doi.org/10.1007/s00467-005-1950-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1014060314

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16047221


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