Common helical V1V2 conformations of HIV-1 Envelope expose the α4β7 binding site on intact virions

Constantinos Kurt Wibmer (), Simone I. Richardson, Jason Yolitz, Claudia Cicala, James Arthos, Penny L. Moore and Lynn Morris
Additional contact information
Constantinos Kurt Wibmer: National Institute for Communicable Diseases (NICD), of the National Health Laboratory Service (NHLS)
Simone I. Richardson: National Institute for Communicable Diseases (NICD), of the National Health Laboratory Service (NHLS)
Jason Yolitz: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Claudia Cicala: National Institute of Allergy and Infectious Diseases, National Institutes of Health
James Arthos: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Penny L. Moore: National Institute for Communicable Diseases (NICD), of the National Health Laboratory Service (NHLS)
Lynn Morris: National Institute for Communicable Diseases (NICD), of the National Health Laboratory Service (NHLS)

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract The α4β7 integrin is a non-essential HIV-1 adhesion receptor, bound by the gp120 V1V2 domain, facilitating rapid viral dissemination into gut-associated lymphoid tissues. Antibodies blocking this interaction early in infection can improve disease outcome, and V1V2-targeted antibodies were correlated with moderate efficacy reported from the RV144 HIV-1 vaccine trial. Monoclonal α4β7-blocking antibodies recognise two slightly different helical V2 conformations, and current structural data suggests their binding sites are occluded in prefusion envelope trimers. Here, we report cocrystal structures of two α4β7-blocking antibodies from an infected donor complexed with scaffolded V1V2 or V2 peptides. Both antibodies recognised the same helix-coil V2 conformation as RV144 antibody CH58, identifying a frequently sampled alternative conformation of full-length V1V2. In the context of Envelope, this α-helical form of V1V2 displays highly exposed α4β7-binding sites, potentially providing a functional role for non-native Envelope on virion or infected cell surfaces in HIV-1 dissemination, pathogenesis, and vaccine design.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06794-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06794-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06794-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().