|
|
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.
 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:
|
|
|
|
 
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]
|
|
|
|
|
