Differential processing of HIV envelope glycans on the virus and soluble recombinant trimer

被引:101
作者
Cao, Liwei [1 ,2 ,3 ,4 ]
Pauthner, Matthias [2 ,3 ,4 ]
Andrabi, Raiees [2 ,3 ,4 ]
Rantalainen, Kimmo [3 ,4 ,5 ]
Berndsen, Zachary [3 ,4 ,5 ]
Diedrich, Jolene K. [1 ]
Menis, Sergey [2 ,3 ,4 ]
Sok, Devin [2 ,3 ,4 ]
Bastidas, Raiza [2 ,3 ,4 ]
Park, Sung-Kyu Robin [1 ]
Delahunty, Claire M. [1 ]
He, Lin [1 ]
Guenaga, Javier [2 ,3 ,4 ]
Wyatt, Richard T. [2 ,3 ,4 ]
Schief, William R. [2 ,3 ,4 ]
Ward, Andrew B. [3 ,4 ,5 ]
Yates, John R., III [1 ]
Burton, Dennis R. [2 ,3 ,4 ,6 ]
Paulson, James C. [1 ,2 ,3 ,4 ]
机构
[1] Scripps Res Inst, Dept Mol Med, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA
[4] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA
[5] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA
[6] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA
来源
NATURE COMMUNICATIONS | 2018年 / 9卷
关键词
BROADLY NEUTRALIZING ANTIBODIES; SITE-SPECIFIC ANALYSIS; DEPENDENT EPITOPE; GLYCOPROTEIN COMPLEX; ENV; PROTEIN; GLYCOSYLATION; SPECIFICITY; MODEL; IDENTIFICATION;
D O I
10.1038/s41467-018-06121-4
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
As the sole target of broadly neutralizing antibodies (bnAbs) to HIV, the envelope glycoprotein (Env) trimer is the focus of vaccination strategies designed to elicit protective bnAbs in humans. Because HIV Env is densely glycosylated with 75-90 N-glycans per trimer, most bnAbs use or accommodate them in their binding epitope, making the glycosylation of recombinant Env a key aspect of HIV vaccine design. Upon analysis of three HIV strains, we here find that site-specific glycosylation of Env from infectious virus closely matches Envs from corresponding recombinant membrane-bound trimers. However, viral Envs differ significantly from recombinant soluble, cleaved (SOSIP) Env trimers, strongly impacting antigenicity. These results provide a benchmark for virus Env glycosylation needed for the design of soluble Env trimers as part of an overall HIV vaccine strategy.
引用
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页数:14
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共 68 条
  • [51] UCSF chimera - A visualization system for exploratory research and analysis
    Pettersen, EF
    Goddard, TD
    Huang, CC
    Couch, GS
    Greenblatt, DM
    Meng, EC
    Ferrin, TE
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 2004, 25 (13) : 1605 - 1612
  • [52] Cell- and Protein-Directed Glycosylation of Native Cleaved HIV-1 Envelope
    Pritchard, Laura K.
    Harvey, David J.
    Bonomelli, Camille
    Crispin, Max
    Doores, Katie J.
    [J]. JOURNAL OF VIROLOGY, 2015, 89 (17) : 8932 - 8944
  • [53] Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers
    Pritchard, Laura K.
    Vasiljevic, Snezana
    Ozorowski, Gabriel
    Seabright, Gemma E.
    Cupo, Albert
    Ringe, Rajesh
    Kim, Helen J.
    Sanders, Rogier W.
    Doores, Katie J.
    Burton, Dennis R.
    Wilson, Ian A.
    Ward, Andrew B.
    Moore, John P.
    Crispin, Max
    [J]. CELL REPORTS, 2015, 11 (10): : 1604 - 1613
  • [54] A Native-Like SOSIP.664 Trimer Based on an HIV-1 Subtype B env Gene
    Pugach, Pavel
    Ozorowski, Gabriel
    Cupo, Albert
    Ringe, Rajesh
    Yasmeen, Anila
    de Val, Natalia
    Derking, Ronald
    Kim, Helen J.
    Korzun, Jacob
    Golabek, Michael
    de los Reyes, Kevin
    Ketas, Thomas J.
    Julien, Jean-Philippe
    Burton, Dennis R.
    Wilson, Ian A.
    Sanders, Rogier W.
    Klasse, P. J.
    Ward, Andrew B.
    Moore, John P.
    [J]. JOURNAL OF VIROLOGY, 2015, 89 (06) : 3380 - 3395
  • [55] A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies
    Sanders, Rogier W.
    Derking, Ronald
    Cupo, Albert
    Julien, Jean-Philippe
    Yasmeen, Anila
    de Val, Natalia
    Kim, Helen J.
    Blattner, Claudia
    de la Pena, Alba Torrents
    Korzun, Jacob
    Golabek, Michael
    de los Reyes, Kevin
    Ketas, Thomas J.
    van Gils, Marit J.
    King, C. Richter
    Wilson, Ian A.
    Ward, Andrew B.
    Klasse, P. J.
    Moore, John P.
    [J]. PLOS PATHOGENS, 2013, 9 (09)
  • [56] Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1
    Sanders, RW
    Vesanen, M
    Schuelke, N
    Master, A
    Schiffner, L
    Kalyanaraman, R
    Paluch, M
    Berkhout, B
    Maddon, PJ
    Olson, WC
    Lu, M
    Moore, JP
    [J]. JOURNAL OF VIROLOGY, 2002, 76 (17) : 8875 - 8889
  • [57] The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120
    Sanders, RW
    Venturi, M
    Schiffner, L
    Kalyanaraman, R
    Katinger, H
    Lloyd, KO
    Kwong, PD
    Moore, JP
    [J]. JOURNAL OF VIROLOGY, 2002, 76 (14) : 7293 - 7305
  • [58] A Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans
    Sok, Devin
    Pauthner, Matthias
    Briney, Bryan
    Lee, Jeong Hyun
    Saye-Francisco, Karen L.
    Hsueh, Jessica
    Ramos, Alejandra
    Le, Khoa M.
    Jones, Meaghan
    Jardine, Joseph G.
    Bastidas, Raiza
    Sarkar, Anita
    Liang, Chi-Hui
    Shivatare, Sachin S.
    Wu, Chung-Yi
    Schief, William R.
    Wong, Chi-Huey
    Wilson, Ian A.
    Ward, Andrew B.
    Zhu, Jiang
    Poignard, Pascal
    Burton, Dennis R.
    [J]. IMMUNITY, 2016, 45 (01) : 31 - 45
  • [59] Stavenhagen K, 2013, J MASS SPECTROM, V48, P627, DOI [10.1002/jms.3210, 10.1002/jms.3189]
  • [60] l Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G
    Stewart-Jones, Guillaume B. E.
    Soto, Cinque
    Lemmin, Thomas
    Chuang, Gwo-Yu
    Druz, Aliaksandr
    Kong, Rui
    Thomas, Paul V.
    Wagh, Kshitij
    Zhou, Tongqing
    Behrens, Anna-Janina
    Bylund, Tatsiana
    Choi, Chang W.
    Davison, Jack R.
    Georgiev, Ivelin S.
    Joyce, M. Gordon
    Do Kwon, Young
    Pancera, Marie
    Taft, Justin
    Yang, Yongping
    Zhang, Baoshan
    Shivatare, Sachin S.
    Shivatare, Vidya S.
    Lee, Chang-Chun D.
    Wu, Chung-Yi
    Bewley, Carole A.
    Burton, Dennis R.
    Koff, Wayne C.
    Connors, Mark
    Crispin, Max
    Baxa, Ulrich
    Korber, Bette T.
    Wong, Chi-Huey
    Mascola, John R.
    Kwong, Peter D.
    [J]. CELL, 2016, 165 (04) : 813 - 826