Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120

Lei Chen; Young Do Kwon; Tongqing Zhou; Xueling Wu; Sijy O'Dell; Lisa Cavacini; Ann J. Hessell; Marie Pancera; Min Tang; Ling Xu; Zhi Yong Yang; Mei Yun Zhang; James Arthos; Dennis R. Burton; Dimiter S. Dimitrov; Gary J. Nabel; Marshall R. Posner; Joseph Sodroski; Richard Wyatt; John R. Mascola; Peter D. Kwong

doi:10.1126/science.1175868

Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120

Lei Chen, Young Do Kwon, Tongqing Zhou, Xueling Wu, Sijy O'Dell, Lisa Cavacini, Ann J. Hessell, Marie Pancera, Min Tang, Ling Xu, Zhi Yong Yang, Mei Yun Zhang, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Gary J. Nabel, Marshall R. Posner, Joseph Sodroski, Richard Wyatt, John R. MascolaPeter D. Kwong

Research output: Contribution to journal › Article › peer-review

257 Scopus citations

Abstract

The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies.

Original language	English (US)
Pages (from-to)	1123-1127
Number of pages	5
Journal	Science
Volume	326
Issue number	5956
DOIs	https://doi.org/10.1126/science.1175868
State	Published - Nov 20 2009
Externally published	Yes

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Chen, L., Do Kwon, Y., Zhou, T., Wu, X., O'Dell, S., Cavacini, L., Hessell, A. J., Pancera, M., Tang, M., Xu, L., Yang, Z. Y., Zhang, M. Y., Arthos, J., Burton, D. R., Dimitrov, D. S., Nabel, G. J., Posner, M. R., Sodroski, J., Wyatt, R., ... Kwong, P. D. (2009). Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science, 326(5956), 1123-1127. https://doi.org/10.1126/science.1175868

Chen, L, Do Kwon, Y, Zhou, T, Wu, X, O'Dell, S, Cavacini, L, Hessell, AJ, Pancera, M, Tang, M, Xu, L, Yang, ZY, Zhang, MY, Arthos, J, Burton, DR, Dimitrov, DS, Nabel, GJ, Posner, MR, Sodroski, J, Wyatt, R, Mascola, JR & Kwong, PD 2009, 'Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120', Science, vol. 326, no. 5956, pp. 1123-1127. https://doi.org/10.1126/science.1175868

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title = "Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120",

abstract = "The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies.",

author = "Lei Chen and {Do Kwon}, Young and Tongqing Zhou and Xueling Wu and Sijy O'Dell and Lisa Cavacini and Hessell, {Ann J.} and Marie Pancera and Min Tang and Ling Xu and Yang, {Zhi Yong} and Zhang, {Mei Yun} and James Arthos and Burton, {Dennis R.} and Dimitrov, {Dimiter S.} and Nabel, {Gary J.} and Posner, {Marshall R.} and Joseph Sodroski and Richard Wyatt and Mascola, {John R.} and Kwong, {Peter D.}",

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AU - Hessell, Ann J.

AU - Pancera, Marie

AU - Tang, Min

AU - Xu, Ling

AU - Yang, Zhi Yong

AU - Zhang, Mei Yun

AU - Arthos, James

AU - Burton, Dennis R.

AU - Dimitrov, Dimiter S.

AU - Nabel, Gary J.

AU - Posner, Marshall R.

AU - Sodroski, Joseph

AU - Wyatt, Richard

AU - Mascola, John R.

AU - Kwong, Peter D.

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Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120

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