PMID: 9420253Jan 7, 1998Paper

Spontaneous mutations in the env gene of the human immunodeficiency virus type 1 NDK isolate are associated with a CD4-independent entry phenotype

Journal of Virology
J DumonceauxU Hazan

Abstract

Human immunodeficiency virus type 1 (HIV-1) entry into target cells is a multistep process initiated by envelope protein gp120 binding to cell surface CD4. The conformational changes induced by this interaction likely favor a second-step interaction between gp120 and a coreceptor such as CXCR4 or CCR5. Here, we report a spontaneous and stable CD4-independent entry phenotype for the HIV-1 NDK isolate. This mutant strain, which emerged from a population of chronically infected CD4-positive CEM cells, can replicate in CD4-negative human cell lines. The presence of CXCR4 alone renders cells susceptible to infection by the mutant NDK, and infection can be blocked by the CXCR4 natural ligand SDF-1. Furthermore, we have correlated the CD4-independent phenotype with seven mutations in the C2 and C3 regions and the V3 loop. We propose that the mutant gp120 spontaneously acquires a conformation allowing it to interact directly with CXCR4. This virus provides us with a powerful tool to study directly gp120-CXCR4 interactions.

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Citations

May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·T L HoffmanR W Doms
Aug 3, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Uriel HazanFrance Pietri-Rouxel
Jan 31, 2003·AIDS·Elaine R ThomasAine McKnight
Feb 24, 2005·AIDS Research and Human Retroviruses·Oliver HartleyJohn P Moore
Aug 3, 2006·The Journal of Biological Chemistry·Abdul A WaheedEric O Freed
Nov 23, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Miao-Ping ChienDing-Kwo Chang
Oct 24, 2008·Molecular Biology of the Cell·Fabien PerugiClaudine Pique
Jan 13, 2012·Current HIV/AIDS Reports·Kathryn Twigg ArrildtRonald Swanstrom
Jan 11, 2013·Advances in Virology·Yoshinao KuboNaoki Yamamoto
Mar 5, 2016·Journal of Virology·Adrienne E SwanstromJames A Hoxie
Feb 17, 2017·Journal of Virology·Yudong QuanMark A Wainberg
Sep 17, 1998·FEBS Letters·L Margolis
Jun 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·T LehnerC Kelly
Sep 10, 2003·Journal of Leukocyte Biology·Kurt Vermeire, Dominique Schols
Jan 10, 2002·AIDS Research and Human Retroviruses·F S De SilvaS Sharma
Jul 10, 2004·AIDS Research and Human Retroviruses·Zhiwei WuDaniel Malamud
Sep 9, 2006·Annual Review of Medicine·Athe M N Tsibris, Daniel R Kuritzkes
Dec 26, 2012·Proceedings of the National Academy of Sciences of the United States of America·Joel R MeyersonSriram Subramaniam
Sep 25, 1999·The Journal of Biological Chemistry·T MirzabekovJ Sodroski
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Jan 31, 2002·Annual Review of Medicine·Welkin E Johnson, Ronald C Desrosiers
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Aine McKnight, Robin A Weiss

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