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Distribution and three-dimensional structure of AIDS virus envelope spikes

Nature volume 441, pages 847852 (15 June 2006) | Download Citation



Envelope glycoprotein (Env) spikes on AIDS retroviruses initiate infection of host cells and are therefore targets for vaccine development. Though crystal structures for partial Env subunits are known, the structure and distribution of native Env spikes on virions is obscure. We applied cryoelectron microscopy tomography to define ultrastructural details of spikes. Virions of wild-type human immunodeficiency virus 1 (HIV-1) and a mutant simian immunodeficiency virus (SIV) had 14 and 73 spikes per particle, respectively, with some clustering of HIV-1 spikes. Three-dimensional averaging showed that the surface glycoprotein (gp120) ‘head’ of each subunit of the trimeric SIV spike contains a primary mass, with two secondary lobes. The transmembrane glycoprotein ‘stalk’ of each trimer is composed of three independent legs that project obliquely from the trimer head, tripod-like. Reconciling available atomic structures with the three-dimensional whole spike density map yields insights into the orientation of Env spike structural elements and possible structural bases of their functions.

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We thank H. Winkler for assistance with volume alignment and classification and 3D volume pickup and P. D. Kwong for his comments on the manuscript. The work was supported in part by a NIH and NCI contract (J.B., E.C., J.D.L.) and grants from the NIH NIAID (P.Z., H.G., K.H.R.) and the NIH NIGMS (J.L., K.A.T.). This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.Author Contributions P.Z. performed the bulk of the cryoEM, image analysis, model fitting, and graphic illustration. J.L. assisted with the image acquisition, analysis and interpretation. J.B. cultured and purified the viruses. E.C. biochemically analysed the virus preparations for purity. J.D.L. contributed to the design of the project and contributed extensively to the manuscript writing. H.G. assisted with fitting of the 2F5 and 4E10 peptides and MAbs into the cryoEM density map. G.A.O. contributed to the analysis of the data, particularly as it relates to the transmembrane region of the envelope spike. K.A.T. provided technical expertise on various aspects of the cryoEM and tomography and contributed to technical portions of the manuscript. K.H.R. provided overall management of the project as well as data interpretation, manuscript writing and figure design.

Author information


  1. Department of Biological Science and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306, USA

    • Ping Zhu
    • , Jun Liu
    • , Henry Grisé
    • , Kenneth A. Taylor
    •  & Kenneth H. Roux
  2. AIDS Vaccine Program, SAIC Frederick Inc, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA

    • Julian Bess Jr
    • , Elena Chertova
    •  & Jeffrey D. Lifson
  3. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

    • Gilad A. Ofek


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Competing interests

Reprints and permissions information is available at The authors declare no competing financial interests.

Corresponding author

Correspondence to Kenneth H. Roux.

Supplementary information

Word documents

  1. 1.

    Supplementary Notes

    This file contains Supplementary Methods, Supplementary Figure Legends, and Supplementary Movie Legends and additional references.

Image files

  1. 1.

    Supplementary Figure 1

    Distribution of inter-spike centre-to-centre distances for mutant SIV and wtHIV-1.

  2. 2.

    Supplementary Figure 2

    Distribution of Env spike cluster sizes on 40 HIV-1 virions compared with the distribution of clusters on hypothetical model virions with randomly placed Env spikes calculated, as described for Supplementary Figure 1.

  3. 3.

    Supplementary Figure 3

    Inherent three-fold symmetry in Env spike averaged images.

  4. 4.

    Supplementary Figure 4

    Z-stack of 42 sequential density sections through the 3-fold axis of the final Env spike average.

  5. 5.

    Supplementary Figure 5

    Comparison of gp120 fitted trimer models.

  6. 6.

    Supplementary Figure 6

    Density distribution profile of the cryoEM trimer slice through the final Env spike average showing the minimum separation between distinguishable internal density peaks measuring 3.2 nm.


  1. 1.

    Supplementary Movie 1

    CryoEM tomogram of SIV virions and corresponding isosurface model.

  2. 2.

    Supplementary Movie 2

    CryoEM spike Env model.

  3. 3.

    Supplementary Movie 3

    De novo fitting of gp120 atomic model into cryoEM isosurface model.

  4. 4.

    Supplementary Movie 4

    CryoEM isosurface model manually fitted with gp41 peptides and docked with MAbs.

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