Abstract
The human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein forms trimers that mediate interactions with the CD4 receptor and a co-receptor on the target cell surface, thereby triggering viral fusion with the cell membrane. Cleavage of Env into its surface, gp120, and transmembrane, gp41, moieties is necessary for activation of its fusogenicity. Here, we produced pseudoviruses with phenotypically mixed wild-type (Wt) and mutant, cleavage-incompetent Env in order to quantify the effects of incorporating uncleaved Env on virion infectivity, antigenicity and neutralization sensitivity. We modeled the relative infectivity of three such phenotypically mixed viral strains, JR-FL, HXBc2 and a derivative of the latter, 3.2P, as a function of the relative amount of Wt Env. The data were fit very closely (R(2) > 0.99) by models which assumed that only Wt homotrimers were functional, with different approximate thresholds of critical numbers of functional trimers per virion for the three strains. We also produced 3.2P pseudoviruses containing both a cleavage-competent Env that is defective for binding the neutralizing monoclonal antibody (NAb) 2G12, and a cleavage-incompetent Env that binds 2G12. The 2G12 NAb was not able t...Continue Reading
References
Nov 11, 1994·Science·D R BurtonP L Nara
Nov 21, 1998·AIDS Research and Human Retroviruses·O S LundJ E Hansen
Apr 6, 1999·The Journal of Cell Biology·A R RosenbergM C Dokhélar
Dec 3, 1999·Science·L EllgaardA Helenius
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·T Murakami, E O Freed
Jan 7, 2000·Journal of Virology·J M BinleyJ P Moore
Apr 25, 2000·Journal of Virology·X YangR Wyatt
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·K Salzwedel, E A Berger
Nov 7, 2000·Biochimica Et Biophysica Acta·M Moulard, E Decroly
Apr 5, 2001·Journal of Virology·Z SiJ Sodroski
Jun 20, 2001·Journal of Virology·P ZhuK H Roux
Jul 13, 2001·Virology·Y IwataniH Sakai
Aug 22, 2001·The Journal of Biological Chemistry·C W ZhangE L Reinherz
Sep 1, 2001·Biochimie·A Land, I Braakman
Sep 6, 2001·The Journal of Biological Chemistry·R K PlemperR Cattaneo
Feb 28, 2002·Journal of Virology·Indresh K SrivastavaSusan W Barnett
Apr 5, 2002·Journal of Virology·Xinzhen YangJoseph Sodroski
May 7, 2002·Journal of Virology·Bimal K ChakrabartiGary J Nabel
Jul 5, 2002·Journal of Virology·Norbert SchülkeWilliam C Olson
Dec 13, 2002·Journal of Virology·Pascal PoignardDennis R Burton
Dec 28, 2002·Journal of Virology·Carolina HerreraJohn P Moore
Apr 3, 2003·Nature Reviews. Molecular Cell Biology·Peter M Colman, Michael C Lawrence
Apr 12, 2003·AIDS Research and Human Retroviruses·Zhihai SiJoseph Sodroski
May 3, 2003·Virology·Stephan BourKlaus Strebel
Jul 23, 2003·Biochimica Et Biophysica Acta·Stephen A GalloRobert Blumenthal
Nov 12, 2003·Journal of Virology·Charles M TrubeyDavid E Ott
Dec 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ping ZhuKenneth H Roux
Jun 15, 2004·Journal of Virology·Eloísa YusteRonald C Desrosiers
Jun 23, 2004·Nature Structural & Molecular Biology·John A G BriggsMarc C Johnson
Jan 22, 2005·Virology·Marie Pancera, Richard Wyatt
Jun 4, 2005·Virology·Carolina HerreraSimon Beddows
Citations
Sep 18, 2013·Journal of Immunological Methods·Carsten MagnusRoland R Regoes
Jan 1, 2014·Advanced Biology·P J Klasse
Oct 13, 2006·Journal of Virology·Wu Ou, Jonathan Silver
Nov 21, 2008·Journal of Virology·Carsten MagnusRoland R Regoes
May 1, 2007·Current Opinion in HIV and AIDS·David C MontefioriJohn R Mascola
Aug 13, 2009·Retrovirology·Karl Salzwedel, Edward A Berger
May 14, 2010·Journal of Virology·Pengcheng Wang, Xinzhen Yang
Dec 3, 2014·Virology·Melissa Zarr, Robert Siliciano
Oct 16, 2007·Vaccine·Jason HammondsPaul Spearman
Nov 7, 2015·Trends in Microbiology·Oliver F BrandenbergAlexandra Trkola
Mar 31, 2007·Current Opinion in Structural Biology·Kenneth H Roux, Kenneth A Taylor
Nov 30, 2006·Virus Research·Mélanie WelmanEric A Cohen
Sep 25, 2015·Retrovirology·Daniel J StiehRobin J Shattock
Oct 25, 2011·Virology·Thomas J KetasPer Johan Klasse
Aug 31, 2013·PloS One·Johannes S GachMichael B Zwick
Sep 11, 2007·Virology·Per Johan Klasse
Jun 5, 2013·Biology·William J Allen, Robert C Rizzo
May 1, 2010·Viruses·Michael A LobritzEric J Arts
Nov 10, 2017·Journal of Virology·Briana QuitadamoPaul R Clapham