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Adaptation of HIV-1 envelope gp120 to humoral immunity at a population level

Nature Medicine volume 16, pages 995–997 (2010)Cite this article

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Abstract

By comparing HIV-1 variants from people who became infected at the beginning of the epidemic and from people who have recently contracted the virus, we observed an enhanced resistance of the virus to antibody neutralization over time, accompanied by an increase in the length of the variable loops and in the number of potential N-linked glycosylation sites on the HIV-1 envelope gp120 subunit. The enhanced neutralization resistance of HIV-1 in contemporary seroconverters coincided with the poorer elicitation of neutralizing antibody responses, which may have implications for vaccine design.

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Figure 1: Increased neutralization resistance and reduced immunogenicity of contemporary subtype B HIV-1 as compared to historical HIV-1 isolates.
Figure 2: Increased Env length and increased number of PNGSs in the viral envelope in contemporary subtype B HIV-1 as compared to historical isolates.

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Acknowledgements

The Amsterdam Cohort Studies on HIV infection and AIDS, a collaboration between the Amsterdam Health Service, the Academic Medical Center of the University of Amsterdam, Sanquin Blood Supply Foundation, the University Medical Center Utrecht and the Jan van Goyen Clinic are part of The Netherlands HIV Monitoring Foundation and are financially supported by the Center for Infectious Disease Control of The Netherlands National Institute for Public Health and the Environment. This study was financially supported by the Dutch AIDS fund (grant 2004064), The Netherlands Organization for Scientific research (grant 918.66.628), an Academic Medical Center graduate school PhD scholarship (M.R.A.W.), the European Community's Six Framework Programme European HIV Enterprise (EUROPRISE; FP6/2007–2012) under grant agreement 037611 and the European Community's Seventh Framework Programme Next Generation HIV-1 Immunogens inducing broadly reactive Neutralizing antibodies (NGIN) (FP7/2007–2013) under grant agreement 201433. We thank the International Antiviral Therapy Evaluation Center for providing financial support for the follow-up of contemporary seroconverters, D. Burton and A. Hessell (The Scripps Research Institute) for their generous supply of IgG1b12, D. Katinger (Polymun, as a partner in EUROPRISE) for his supply of mAbs 2G12, 2F5 and 4E10, and D. Montefiori (Duke University Medical Center) for his supply of HIVIg. The following reagents were obtained through the US National Institutes of Health AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases: HIV-IG from North American Biologicals and the National Heart, Lung, and Blood Institute.

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  1. Matthijs R A Welkers & Hanneke Schuitemaker

    Present address: Present addresses: Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (M.R.A.W.) and Crucell Holland BV, Leiden, The Netherlands (H.S.).,

  2. Zelda Euler and Matthijs R A Welkers: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Evelien M Bunnik, Zelda Euler, Matthijs R A Welkers, Brigitte D M Boeser-Nunnink & Hanneke Schuitemaker

  2. Department of Infectious Diseases, Tropical Medicine and AIDS, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Marlous L Grijsen & Jan M Prins

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  1. Evelien M Bunnik
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Contributions

E.M.B. designed the study, performed experiments, analyzed data and wrote the manuscript; Z.E. performed experiments and analyzed data; M.R.A.W. performed part of the sequence analyses; B.D.M.B.-N. performed part of the neutralization experiments; M.L.G. and J.M.P. selected and recruited individuals for the contemporary seroconverter cohort and contributed samples and data of these subjects; and H.S. designed the study, supervised the project and wrote the manuscript.

Corresponding author

Correspondence to Hanneke Schuitemaker.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3, Table 1 and Methods (PDF 161 kb)

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Bunnik, E., Euler, Z., Welkers, M. et al. Adaptation of HIV-1 envelope gp120 to humoral immunity at a population level. Nat Med 16, 995–997 (2010). https://doi.org/10.1038/nm.2203

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