Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions

James B Munro; Jason Gorman; Xiaochu Ma; Zhou Zhou; James Arthos; Dennis R Burton; Wayne C Koff; Joel R Courter; Amos B Smith 3rd; Peter D Kwong; Scott C Blanchard; Walther Mothes

doi:10.1126/science.1254426

Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions

Science. 2014 Nov 7;346(6210):759-63. doi: 10.1126/science.1254426. Epub 2014 Oct 8.

Authors

Affiliations

¹ Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA. walther.mothes@yale.edu scb2005@med.cornell.edu james.munro@tufts.edu.
² Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
³ Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
⁴ Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA.
⁵ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Department of Immunology and Microbial Science, and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA.
⁷ International AIDS Vaccine Initiative (IAVI), New York, NY 10004, USA.
⁸ Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹ Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA. walther.mothes@yale.edu scb2005@med.cornell.edu james.munro@tufts.edu.

Abstract

The HIV-1 envelope (Env) mediates viral entry into host cells. To enable the direct imaging of conformational dynamics within Env, we introduced fluorophores into variable regions of the glycoprotein gp120 subunit and measured single-molecule fluorescence resonance energy transfer within the context of native trimers on the surface of HIV-1 virions. Our observations revealed unliganded HIV-1 Env to be intrinsically dynamic, transitioning between three distinct prefusion conformations, whose relative occupancies were remodeled by receptor CD4 and antibody binding. The distinct properties of neutralization-sensitive and neutralization-resistant HIV-1 isolates support a dynamics-based mechanism of immune evasion and ligand recognition.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Antibodies, Neutralizing / immunology
CD4 Antigens / immunology
Fluorescence Resonance Energy Transfer / methods
HIV Envelope Protein gp120 / chemistry*
HIV Envelope Protein gp120 / immunology
HIV-1 / chemistry*
HIV-1 / immunology
Humans
Immune Evasion*
Ligands
Models, Chemical
Molecular Imaging / methods
Protein Multimerization
Protein Structure, Tertiary
Virion / chemistry*
Virion / immunology

Substances

Antibodies, Neutralizing
CD4 Antigens
HIV Envelope Protein gp120
Ligands

Abstract

Publication types

MeSH terms

Substances

Grants and funding