PMID: 26051934
Title: Structural Constraints Determine the Glycosylation of HIV 1 Envelope Trimers
Abstract: A highly glycosylated, trimeric envelope glycoprotein (Env) mediates HIV-1 cell entry. The high density and heterogeneity of the glycans shield Env from recognition by the immune system, but paradoxically, many potent broadly neutralizing antibodies (bNAbs) recognize epitopes involving this glycan shield. To better understand Env glycosylation and its role in bNAb recognition, we characterized a soluble, cleaved recombinant trimer (BG505 SOSIP.664) that is a close structural and antigenic mimic of native Env. Large, unprocessed oligomannose-type structures (Man8-9GlcNAc2) are notably prevalent on the gp120 components of the trimer, irrespective of the mammalian cell expression system or the bNAb used for affinity purification. In contrast, gp41 subunits carry more highly processed glycans. The glycans on uncleaved, non-native oligomeric gp140 proteins are also highly processed. A homogeneous, oligomannose-dominated glycan profile is therefore a hallmark of a native Env conformation and a potential Achilles' heel that can be exploited for bNAb recognition and vaccine design.
Date: 1970-08-22
Year: 2016
Journal: Cell Rep
PMID Author: Pritchard LK, Vasiljevic S, Ozorowski G, Seabright GE, Cupo A, Ringe R, Kim HJ, Sanders RW, Doores KJ, Burton DR, Wilson IA, Ward AB, Moore JP, Crispin M
PMC Link #: PMC4555872
Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers. Cell Rep 2015;11(10):1604-13 doi: 10.1016/j.celrep.2015.05.017

Media Contacts

Africa

Ethel Makila
+254 71 904 3142
EMakila@iavi.org

 

Europe

Hester Kuipers
+31 20 521 0343
HKuipers@iavi.org 

 

India

Saif ul Hadi
+91 11 4737 6032
SulHadi@iavi.org 

 

United States

Rose Catlos
+1 212 847 1049
RCatlos@iavi.org