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

页数：14

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