The University of Southampton
University of Southampton Institutional Repository

Similarities and differences between native HIV-1 envelope glycoprotein trimers and stabilized soluble trimer mimetics

Similarities and differences between native HIV-1 envelope glycoprotein trimers and stabilized soluble trimer mimetics
Similarities and differences between native HIV-1 envelope glycoprotein trimers and stabilized soluble trimer mimetics

The HIV-1 envelope glycoprotein (Env) trimer is located on the surface of the virus and is the target of broadly neutralizing antibodies (bNAbs). Recombinant native-like soluble Env trimer mimetics, such as SOSIP trimers, have taken a central role in HIV-1 vaccine research aimed at inducing bNAbs. We therefore performed a direct and thorough comparison of a full-length unmodified Env trimer containing the transmembrane domain and the cytoplasmic tail, with the sequence matched soluble SOSIP trimer, both based on an early Env sequence (AMC011) from an HIV+ individual that developed bNAbs. The structures of the full-length AMC011 trimer bound to either bNAb PGT145 or PGT151 were very similar to the structures of SOSIP trimers. Antigenically, the full-length and SOSIP trimers were comparable, but in contrast to the full-length trimer, the SOSIP trimer did not bind at all to non-neutralizing antibodies, most likely as a consequence of the intrinsic stabilization of the SOSIP trimer. Furthermore, the glycan composition of full-length and SOSIP trimers was similar overall, but the SOSIP trimer possessed slightly less complex and less extensively processed glycans, which may relate to the intrinsic stabilization as well as the absence of the membrane tether. These data provide insights into how to best use and improve membrane-associated full-length and soluble SOSIP HIV-1 Env trimers as immunogens.

1553-7366
Torrents de la Peña, Alba
5aa8f573-c651-4d0d-b816-93544ea46457
Rantalainen, Kimmo
d86844e5-562c-482f-b872-d03eb1631da0
Cottrell, Christopher A.
942bfa7b-c09e-459d-a6c2-0d64d55fa230
Allen, Joel D.
c873d886-2a66-475b-ae04-57a10b37e716
van Gils, Marit J.
f2e1e7f1-36a1-4270-8509-d17a10ddb9a6
Torres, Jonathan L.
8e9a3e7b-a841-4748-927b-967ac8135774
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Sanders, Rogier W.
d3b67c2c-c725-42e7-b972-50b30be67c74
Ward, Andrew B.
78ce5b6a-b852-4ee4-a950-f7ff7b183d83
Torrents de la Peña, Alba
5aa8f573-c651-4d0d-b816-93544ea46457
Rantalainen, Kimmo
d86844e5-562c-482f-b872-d03eb1631da0
Cottrell, Christopher A.
942bfa7b-c09e-459d-a6c2-0d64d55fa230
Allen, Joel D.
c873d886-2a66-475b-ae04-57a10b37e716
van Gils, Marit J.
f2e1e7f1-36a1-4270-8509-d17a10ddb9a6
Torres, Jonathan L.
8e9a3e7b-a841-4748-927b-967ac8135774
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Sanders, Rogier W.
d3b67c2c-c725-42e7-b972-50b30be67c74
Ward, Andrew B.
78ce5b6a-b852-4ee4-a950-f7ff7b183d83

Torrents de la Peña, Alba, Rantalainen, Kimmo, Cottrell, Christopher A., Allen, Joel D., van Gils, Marit J., Torres, Jonathan L., Crispin, Max, Sanders, Rogier W. and Ward, Andrew B. (2019) Similarities and differences between native HIV-1 envelope glycoprotein trimers and stabilized soluble trimer mimetics. PLoS Pathogens, 15 (7), [e1007920]. (doi:10.1371/journal.ppat.1007920).

Record type: Article

Abstract

The HIV-1 envelope glycoprotein (Env) trimer is located on the surface of the virus and is the target of broadly neutralizing antibodies (bNAbs). Recombinant native-like soluble Env trimer mimetics, such as SOSIP trimers, have taken a central role in HIV-1 vaccine research aimed at inducing bNAbs. We therefore performed a direct and thorough comparison of a full-length unmodified Env trimer containing the transmembrane domain and the cytoplasmic tail, with the sequence matched soluble SOSIP trimer, both based on an early Env sequence (AMC011) from an HIV+ individual that developed bNAbs. The structures of the full-length AMC011 trimer bound to either bNAb PGT145 or PGT151 were very similar to the structures of SOSIP trimers. Antigenically, the full-length and SOSIP trimers were comparable, but in contrast to the full-length trimer, the SOSIP trimer did not bind at all to non-neutralizing antibodies, most likely as a consequence of the intrinsic stabilization of the SOSIP trimer. Furthermore, the glycan composition of full-length and SOSIP trimers was similar overall, but the SOSIP trimer possessed slightly less complex and less extensively processed glycans, which may relate to the intrinsic stabilization as well as the absence of the membrane tether. These data provide insights into how to best use and improve membrane-associated full-length and soluble SOSIP HIV-1 Env trimers as immunogens.

Text
journal.ppat.1007920 - Version of Record
Available under License Creative Commons Attribution.
Download (3MB)

More information

Accepted/In Press date: 17 June 2019
e-pub ahead of print date: 15 July 2019

Identifiers

Local EPrints ID: 432940
URI: http://eprints.soton.ac.uk/id/eprint/432940
ISSN: 1553-7366
PURE UUID: 6d694f5a-4ef7-4661-ad12-fc74009a26b0
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 01 Aug 2019 16:30
Last modified: 07 Oct 2020 02:15

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×