DOI: 10.1073/pnas.2634931100. Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions

Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions

10.1073/pnas.2634931100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We used electron tomography to directly visualize trilobed presumptive envelope (env) glycoprotein structures on the surface of negatively stained HIV type 1 (HIV-1) and simian immunodeficiency virus (SIV) virions. Wild–type HIV-1 and SIV virions had an average of 8–10 trimers per virion, consistent with predictions based on biochemical evidence. Mutant SIVs, biochemically demonstrated to contain high levels of the viral env proteins, averaged 70–79 trimers per virion in tomograms. These correlations strongly indicate that the visualized trimers represent env spikes. The env trimers were without obvious geometric distribution pattern or preferred rotational orientation. Combined with biochemical analysis of gag/env ratios in virions, these trimer counts allow calculation of the number of gag molecules per virion, yielding an average value of ≈1,400. Virion and env dimensions were also determined. Image-averaging analysis of SIV env trimers revealed a distinct chirality and strong concordance with recent molecular models. The results directly demonstrate the presence of env trimers on the surface of AIDS virus virions, albeit at numbers much lower than generally appreciated, and have important implications for understanding virion formation, virus interactions with host cells, and virus neutralization.

Bibliography

Zhu, P., Chertova, E., Bess, J., Lifson, J. D., Arthur, L. O., Liu, J., Taylor, K. A., & Roux, K. H. (2003). Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Proceedings of the National Academy of Sciences, 100(26), 15812â15817.

Authors 8

Ping Zhu (first)
Elena Chertova (additional)
Julian Bess (additional)
Jeffrey D. Lifson (additional)
Larry O. Arthur (additional)
Jun Liu (additional)
Kenneth A. Taylor (additional)
Kenneth H. Roux (additional)

References 42 Referenced 346

10.1021/bi00046a001
10.1038/nsb1295-1075
10.1038/31514
10.1038/31405
10.1126/science.280.5371.1884
10.1128/JVI.74.4.1961-1972.2000
10.1128/JVI.74.15.7005-7015.2000
10.1146/annurev.immunol.19.1.253
10.1128/JVI.76.17.8875-8889.2002
10.1016/S0092-8674(00)80205-6
10.1038/3293
10.1016/S0092-8674(00)81430-0
10.1128/JVI.76.15.7863-7867.2002
10.1073/pnas.261573898
10.1016/0042-6822(87)90449-1
10.1007/BF01487688
10.1007/BF01311033
10.1128/JVI.72.10.7992-8001.1998
Arthur, L. O., Bess, J. W., Jr., Chertova, E. N., Rossio, J. L., Esser, M. T., Benveniste, R. E., Henderson, L. E. & Lifson, J. D. (1998) AIDS Res. Hum. Retroviruses 14, 8311-8319. / AIDS Res. Hum. Retroviruses (1998)
10.1128/JVI.76.11.5315-5325.2002
10.1016/0076-6879(89)78010-1
Radermacher M. (1992) in Electron Tomography ed. Frank J. (Plenum New York) pp. 91-115. (10.1007/978-1-4757-2163-8_5)
10.1126/science.8096089
10.1016/S0092-8674(00)81528-7
10.1006/jsbi.1997.3932
10.1006/jsbi.1996.0013
Frank J. (1996) in Three-Dimensional Electron Microscopy of Macromolecular Assemblies (Academic New York) pp. 1-341. (10.1016/B978-012265040-6/50001-1)
10.1107/S0108767390010224
10.1126/science.1470916
10.1007/BF00430305
10.1128/JVI.75.8.3903-3915.2001
10.1099/0022-1317-70-8-2215
10.1007/BF01310950
10.1093/emboj/17.16.4572
10.1016/S0925-4439(01)00042-4
10.1006/jmbi.2000.3715
10.1016/S0969-2126(00)00547-5
10.1016/0042-6822(92)90593-E
10.1128/jvi.68.8.5264-5269.1994
10.1099/0022-1317-67-11-2533
10.1128/jvi.67.7.3818-3825.1993
10.1128/jvi.70.1.341-351.1996

Dates

Type	When
Created	21 years, 7 months ago (Dec. 23, 2003, 7:58 a.m.)
Deposited	3 years, 3 months ago (April 25, 2022, 5:49 p.m.)
Indexed	3 weeks, 6 days ago (July 24, 2025, 7:22 a.m.)
Issued	21 years, 8 months ago (Dec. 10, 2003)
Published	21 years, 8 months ago (Dec. 10, 2003)
Published Online	21 years, 8 months ago (Dec. 10, 2003)
Published Print	21 years, 7 months ago (Dec. 23, 2003)

Funders 0

None

BibTeX

@article{Zhu_2003, title={Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.2634931100}, DOI={10.1073/pnas.2634931100}, number={26}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Zhu, Ping and Chertova, Elena and Bess, Julian and Lifson, Jeffrey D. and Arthur, Larry O. and Liu, Jun and Taylor, Kenneth A. and Roux, Kenneth H.}, year={2003}, month=dec, pages={15812–15817} }

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