SEARCH:   Advanced

Blood, 1 March 2004, Vol. 103, No. 5, pp. 1586-1594. Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-05-1390. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1390v1 103/5/1586    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Markovic, I. Articles by Clouse, K. A. Search for Related Content PubMed PubMed Citation Articles by Markovic, I. Articles by Clouse, K. A. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry Ingrid Markovic, Tzanko S. Stantchev, Karen H. Fields, Linda J. Tiffany, Melanija Tomiç, Carol D. Weiss, Christopher C. Broder, Klaus Strebel, and Kathleen A. Clouse From the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research, Food and Drug Administration (FDA), Bethesda, MD; F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; and the National Institute of Child Health and Human Diseases and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. Attachment of gp120 to CD4 during HIV-1 entry triggers structural rearrangement in gp120 that enables binding to an appropriate coreceptor. Following coreceptor engagement, additional conformational changes occur in the envelope (Env), resulting in fusion of virion and cell membranes. Catalysts with redox-isomerase activity, such as protein disulfide isomerase (PDI), facilitate Env conversion from its inactive to its fusion-competent conformation. We report here that anti-PDI agents effectively block CXCR4 Env-mediated fusion and spread of virus infection. Exogenously added PDI, in turn, can rescue fusion from this blockade. We further find that PDI facilitates thiol/disulfide rearrangement in gp120 during conformational change, whereas inhibition of this redox shuffling prevents gp41 from assuming the fusogenic 6-helix bundle conformation. At the virus-cell contact site, gp120 induces assembly of PDI, CD4, and CXCR4 into a tetramolecular protein complex serving as a portal for viral entry. Our findings support the hypothesis that Env conformational change depends on a well-coordinated action of a tripartite system in which PDI works in concert with the receptor and the coreceptor to effectively lower the activation energy barrier required for Env conformational rearrangement. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: HIV envelope becomes unhinged by PDI for entry Richard S. Kornbluth Blood 2004 103: 1567. [Full Text] [PDF] Related Letter in Blood Online: HIV Env reduction postreceptor binding: a new target for AIDS treatment? Emmanuel Fenouillet, Rym Barbouche, and Ian M. Jones Blood 2004 104: 296. [Full Text] [PDF] This article has been cited by other articles: S. Jain, L. W. McGinnes, and T. G. Morrison Role of Thiol/Disulfide Exchange in Newcastle Disease Virus Entry J. Virol., January 1, 2009; 83(1): 241 - 249. [Abstract] [Full Text] [PDF] S. Jain, L. W. McGinnes, and T. G. Morrison Overexpression of Thiol/Disulfide Isomerases Enhances Membrane Fusion Directed by the Newcastle Disease Virus Fusion Protein J. Virol., December 15, 2008; 82(24): 12039 - 12048. [Abstract] [Full Text] [PDF] E. van Anken, R. W. Sanders, I. M. Liscaljet, A. Land, I. Bontjer, S. Tillemans, A. A. Nabatov, W. A. Paxton, B. Berkhout, and I. Braakman Only Five of 10 Strictly Conserved Disulfide Bonds Are Essential for Folding and Eight for Function of the HIV-1 Envelope Glycoprotein Mol. Biol. Cell, October 1, 2008; 19(10): 4298 - 4309. [Abstract] [Full Text] [PDF] D. G. Meckes Jr. and J. W. Wills Dynamic Interactions of the UL16 Tegument Protein with the Capsid of Herpes Simplex Virus J. Virol., December 1, 2007; 81(23): 13028 - 13036. [Abstract] [Full Text] [PDF] G. Abou-Jaoude and C. Sureau Entry of Hepatitis Delta Virus Requires the Conserved Cysteine Residues of the Hepatitis B Virus Envelope Protein Antigenic Loop and Is Blocked by Inhibitors of Thiol-Disulfide Exchange J. Virol., December 1, 2007; 81(23): 13057 - 13066. [Abstract] [Full Text] [PDF] J. Billington, T. P. Hickling, G. H. Munro, C. Halai, R. Chung, G. G. Dodson, and R. S. Daniels Stability of a Receptor-Binding Active Human Immunodeficiency Virus Type 1 Recombinant gp140 Trimer Conferred by Intermonomer Disulfide Bonding of the V3 Loop: Differential Effects of Protein Disulfide Isomerase on CD4 and Coreceptor Binding J. Virol., May 1, 2007; 81(9): 4604 - 4614. [Abstract] [Full Text] [PDF] K. Gumireddy, F. Sun, A. J. Klein-Szanto, J. M. Gibbins, P. A. Gimotty, A. J. Saunders, P. G. Schultz, and Q. Huang In vivo selection for metastasis promoting genes in the mouse PNAS, April 17, 2007; 104(16): 6696 - 6701. [Abstract] [Full Text] [PDF] S. Jain, L. W. McGinnes, and T. G. Morrison Thiol/Disulfide Exchange Is Required for Membrane Fusion Directed by the Newcastle Disease Virus Fusion Protein J. Virol., March 1, 2007; 81(5): 2328 - 2339. [Abstract] [Full Text] [PDF] S. M. Wahl, T. Greenwell-Wild, and N. Vazquez HIV accomplices and adversaries in macrophage infection J. Leukoc. Biol., November 1, 2006; 80(5): 973 - 983. [Abstract] [Full Text] [PDF] D. Lavillette, R. Barbouche, Y. Yao, B. Boson, F.-L. Cosset, I. M. Jones, and E. Fenouillet Significant Redox Insensitivity of the Functions of the SARS-CoV Spike Glycoprotein: COMPARISON WITH HIV ENVELOPE J. Biol. Chem., April 7, 2006; 281(14): 9200 - 9204. [Abstract] [Full Text] [PDF] R. M. Markosyan, F. S. Cohen, and G. B. Melikyan Time-resolved Imaging of HIV-1 Env-mediated Lipid and Content Mixing between a Single Virion and Cell Membrane Mol. Biol. Cell, December 1, 2005; 16(12): 5502 - 5513. [Abstract] [Full Text] [PDF] K. M. Copeland, A. J. Elliot, and R. S. Daniels Functional Chimeras of Human Immunodeficiency Virus Type 1 gp120 and Influenza A Virus (H3) Hemagglutinin J. Virol., May 15, 2005; 79(10): 6459 - 6471. [Abstract] [Full Text] [PDF] R. Barbouche, H. Lortat-Jacob, I. M. Jones, and E. Fenouillet Glycosaminoglycans and Protein Disulfide Isomerase-Mediated Reduction of HIV Env Mol. Pharmacol., April 1, 2005; 67(4): 1111 - 1118. [Abstract] [Full Text] [PDF] P. A. Jordan, J. M. Stevens, G. P. Hubbard, N. E. Barrett, T. Sage, K. S. Authi, and J. M. Gibbins A role for the thiol isomerase protein ERP5 in platelet function Blood, February 15, 2005; 105(4): 1500 - 1507. [Abstract] [Full Text] [PDF] E. Fenouillet, R. Barbouche, and I. M. Jones HIV Env reduction postreceptor binding: a new target for AIDS treatment? Blood, July 1, 2004; 104(1): 296 - 296. [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020