A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield

被引：585

作者：

Pejchal, Robert ^{[2
,3
]}

Doores, Katie J. ^{[1
,2
,4
]}

Walker, Laura M. ^{[1
,2
]}

Khayat, Reza ^{[2
,3
]}

Huang, Po-Ssu ^{[5
]}

Wang, Sheng-Kai ^{[6
]}

Stanfield, Robyn L. ^{[2
,3
]}

Julien, Jean-Philippe ^{[2
,3
]}

Ramos, Alejandra ^{[1
,2
]}

Crispin, Max ^{[7
]}

Depetris, Rafael ^{[8
]}

Katpally, Umesh ^{[9
]}

Marozsan, Andre ^{[9
]}

Cupo, Albert ^{[9
]}

Maloveste, Sebastien ^{[10
]}

Liu, Yan ^{[11
]}

McBride, Ryan ^{[12
]}

Ito, Yukishige ^{[13
,14
]}

Sanders, Rogier W. ^{[8
,15
]}

Ogohara, Cassandra ^{[5
]}

Paulson, James C. ^{[12
]}

Feizi, Ten ^{[11
]}

Scanlan, Christopher N. ^{[7
]}

Wong, Chi-Huey ^{[6
]}

Moore, John P. ^{[8
]}

Olson, William C. ^{[9
]}

Ward, Andrew B. ^{[2
,3
]}

Poignard, Pascal ^{[1
,2
,16
]}

Schief, William R. ^{[1
,2
,5
]}

Burton, Dennis R. ^{[1
,2
,4
]}

Wilson, Ian A. ^{[2
,3
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[2] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Mol Biol, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[4] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA

[5] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[6] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[7] Univ Oxford, Dept Biochem, Oxford Glycobiol Inst, Oxford OX1 3QU, England

[8] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[9] Progen Pharmaceut, Tarrytown, NY 10591 USA

[10] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA

[11] Univ London Imperial Coll Sci Technol & Med, Dept Med, Glycosci Lab, London W12 0NN, England

[12] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[13] RIKEN Adv Sci Inst, Wako, Saitama 3510198, Japan

[14] Japan Sci & Technol Agcy, Exploratory Res Adv Technol, Wako, Saitama 3510198, Japan

[15] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[16] Int AIDS Vaccine Initiat, New York, NY 10038 USA

来源：

SCIENCE | 2011年 / 334卷 / 6059期

基金：

英国工程与自然科学研究理事会; 加拿大健康研究院;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN COMPLEX; GP120; PANEL;

D O I：

10.1126/science.1213256

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The HIV envelope (Env) protein gp120 is protected from antibody recognition by a dense glycan shield. However, several of the recently identified PGT broadly neutralizing antibodies appear to interact directly with the HIV glycan coat. Crystal structures of antigen-binding fragments (Fabs) PGT 127 and 128 with Man(9) at 1.65 and 1.29 angstrom resolution, respectively, and glycan binding data delineate a specific high mannose-binding site. Fab PGT 128 complexed with a fully glycosylated gp120 outer domain at 3.25 angstroms reveals that the antibody penetrates the glycan shield and recognizes two conserved glycans as well as a short beta-strand segment of the gp120 V3 loop, accounting for its high binding affinity and broad specificify. Furthermore, our data suggest that the high neutralization potency of PGT 127 and 128 immunoglobulin Gs may be mediated by cross-linking Env trimers on the viral surface.

引用

页码：1097 / 1103

页数：8

共 39 条

[1] Temperature-dependent production of pseudoinfectious dengue reporter virus particles by complementation [J].

Ansarah-Sobrinho, Camilo ;

Nelson, Steevenson ;

Jost, Christiane A. ;

Whitehead, Stephen S. ;

Pierson, Theodore C. .

VIROLOGY, 2008, 381 (01) :67-74

[2] Construction and characterization of soluble, cleaved, and stabilized trimeric Env proteins based on HIV type 1 Env subtype A [J].

Beddows, Simon ;

Kirschner, Marc ;

Campbell-Gardener, Lila ;

Franti, Michael ;

Dey, Antu K. ;

Iyer, Sai Prasad N. ;

Maddon, Paul J. ;

Paluch, Maciej ;

Master, Aditi ;

Overbaugh, Julie ;

VanCott, Thomas ;

Olson, William C. ;

Moore, John P. .

AIDS RESEARCH AND HUMAN RETROVIRUSES, 2006, 22 (06) :569-579

[3] Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies [J].

Binley, JA ;

Wrin, T ;

Korber, B ;

Zwick, MB ;

Wang, M ;

Chappey, C ;

Stiegler, G ;

Kunert, R ;

Zolla-Pazner, S ;

Katinger, H ;

Petropoulos, CJ ;

Burton, DR .

JOURNAL OF VIROLOGY, 2004, 78 (23) :13232-13252

[4] Enhancing the proteolytic maturation of human immunodeficiency virus type 1 envelope glycoproteins [J].

Binley, JM ;

Sanders, RW ;

Master, A ;

Cayanan, CS ;

Wiley, CL ;

Schiffner, L ;

Travis, B ;

Kuhmann, S ;

Burton, DR ;

Hu, SL ;

Olson, WC ;

Moore, JP .

JOURNAL OF VIROLOGY, 2002, 76 (06) :2606-2616

[5] A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure [J].

Binley, JM ;

Sanders, RW ;

Clas, B ;

Schuelke, N ;

Master, A ;

Guo, Y ;

Kajumo, F ;

Anselma, DJ ;

Maddon, PJ ;

Olson, WC ;

Moore, JP .

JOURNAL OF VIROLOGY, 2000, 74 (02) :627-643

[6] Antibody domain exchange is an immunological solution to carbohydrate cluster recognition [J].

Calarese, DA ;

Scanlan, CN ;

Zwick, MB ;

Deechongkit, S ;

Mimura, Y ;

Kunert, R ;

Zhu, P ;

Wormald, MR ;

Stanfield, RL ;

Roux, KH ;

Kelly, JW ;

Rudd, PM ;

Dwek, RA ;

Katinger, H ;

Burton, DR ;

Wilson, IA .

SCIENCE, 2003, 300 (5628) :2065-2071

[7] A Dynamic Landscape for Antibody Binding Modulates Antibody-Mediated Neutralization of West Nile Virus [J].

Dowd, Kimberly A. ;

Jost, Christiane A. ;

Durbin, Anna P. ;

Whitehead, Stephen S. ;

Pierson, Theodore C. .

PLOS PATHOGENS, 2011, 7 (06)

[8] The Neutralization Breadth of HIV-1 Develops Incrementally over Four Years and Is Associated with CD4+ T Cell Decline and High Viral Load during Acute Infection [J].

Gray, Elin S. ;

Madiga, Maphuti C. ;

Hermanus, Tandile ;

Moore, Penny L. ;

Wibmer, Constantinos Kurt ;

Tumba, Nancy L. ;

Werner, Lise ;

Mlisana, Koleka ;

Sibeko, Sengeziwe ;

Williamson, Carolyn ;

Karim, Salim S. Abdool ;

Morris, Lynn .

JOURNAL OF VIROLOGY, 2011, 85 (10) :4828-4840

[9] Soluble CD4 and CD4-Mimetic Compounds Inhibit HIV-1 Infection by Induction of a Short-Lived Activated State [J].

Haim, Hillel ;

Si, Zhihai ;

Madani, Navid ;

Wang, Liping ;

Courter, Joel R. ;

Princiotto, Amy ;

Kassa, Aemro ;

DeGrace, Marciella ;

McGee-Estrada, Kathleen ;

Mefford, Megan ;

Gabuzda, Dana ;

Smith, Amos B., III ;

Sodroski, Joseph .

PLOS PATHOGENS, 2009, 5 (04)

[10] Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope glycoproteins display the same closed and open quaternary molecular architectures [J].

Harris, Audray ;

Borgnia, Mario J. ;

Shi, Dan ;

Bartesaghi, Alberto ;

He, Haifeng ;

Pejchal, Robert ;

Kang, Yun ;

Depetris, Rafael ;

Marozsan, Andre J. ;

Sanders, Rogier W. ;

Klasse, Per Johan ;

Milne, Jacqueline L. S. ;

Wilson, Ian A. ;

Olson, William C. ;

Moore, John P. ;

Subramaniam, Sriram .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (28) :11440-11445

← 1 2 3 4 →