Quantification of the Resilience and Vulnerability of HIV-1 Native Glycan Shield at Atomistic Detail

Srirupa Chakraborty; Zachary T Berndsen; Nicolas W Hengartner; Bette T Korber; Andrew B Ward; S Gnanakaran

doi:10.1016/j.isci.2020.101836

Quantification of the Resilience and Vulnerability of HIV-1 Native Glycan Shield at Atomistic Detail

iScience. 2020 Nov 20;23(12):101836. doi: 10.1016/j.isci.2020.101836. eCollection 2020 Dec 18.

Authors

Srirupa Chakraborty^{1

2}, Zachary T Berndsen^{3

4}, Nicolas W Hengartner¹, Bette T Korber¹, Andrew B Ward^{3

4}, S Gnanakaran¹

Affiliations

¹ Theoretical Biology & Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
² Center for Non-Linear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
³ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁴ IAVI Neutralizing Antibody Center and Collaboration of AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

Dense surface glycosylation on the HIV-1 envelope (Env) protein acts as a shield from the adaptive immune system. However, the molecular complexity and flexibility of glycans make experimental studies a challenge. Here we have integrated high-throughput atomistic modeling of fully glycosylated HIV-1 Env with graph theory to capture immunologically important features of the shield topology. This is the first complete all-atom model of HIV-1 Env SOSIP glycan shield that includes both oligomannose and complex glycans, providing physiologically relevant insights of the glycan shield. This integrated approach including quantitative comparison with cryo-electron microscopy data provides hitherto unexplored details of the native shield architecture and its difference from the high-mannose glycoform. We have also derived a measure to quantify the shielding effect over the antigenic protein surface that defines regions of relative vulnerability and resilience of the shield and can be harnessed for rational immunogen design.

Keywords: HIV Glycan Shield; Molecular Modeling; Virology.

Abstract

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