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Distinct antibody-mediated selection in a narrow-source HIV-1 outbreak among Chinese former plasma donors

Sophie M. Andrews, Yonghong Zhang, Tao Dong, Sarah L. Rowland-Jones, Sunetra Gupta, Joakim ESBJÖRNSSON
doi: https://doi.org/10.1101/167510
Sophie M. Andrews
1Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. E-mail:
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  • For correspondence: sophie.andrews@ndm.ox.ac.uk
Yonghong Zhang
2Beijing You’an Hospital, Capital Medical University, Beijing, China. E-mail:
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  • For correspondence: 13810108505@163.com
Tao Dong
3Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. E-mail:
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  • For correspondence: tao.dong@imm.ox.ac.uk
Sarah L. Rowland-Jones
4Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. E-mail:
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  • For correspondence: sarah.rowland-jones@ndm.ox.ac.uk
Sunetra Gupta
5Department of Zoology, University of Oxford, Oxford, United Kingdom. E-mail:
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  • For correspondence: sunetra.gupta@zoo.ox.ac.uk
Joakim ESBJÖRNSSON
6Nuffield Department of Medicine, University of Oxford, NDMRB, Old Road Campus, Roosevelt Drive, Headington, Oxfordshire, United Kingdom, OX3 7FZ.
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  • For correspondence: joakim.esbjornsson@ndm.ox.ac.uk
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ABSTRACT

The HIV-1 envelope protein mutates rapidly to evade recognition and killing, and is a major target of the humoral immune response and in vaccine development. Identification of common antibody epitopes for vaccine development have been complicated by large variations on both virus (different infecting founder strains) and host genetic levels. We studied HIV-1 envelope gp120 evolution in 12 Chinese former plasma donors infected with a purportedly single founder virus, with the aim of identifying common antibody epitopes under immune selection. We found five amino acid sites to be under significant positive selection in ≥50% of the patients, and 22 sites housing mutations consistent with antibody-mediated selection. Despite strong selection pressure, some sites housed a limited repertoire of amino acids. Structural modelling revealed that most sites were located on the exposed distal edge of the Gp120 trimer, whilst wholly invariant sites clustered within the centre of the protein complex. Four sites, flanking the V3 hypervariable loop of the Gp120, represent novel antibody epitopes that may be suitable as vaccine candidates.

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Posted July 24, 2017.
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Distinct antibody-mediated selection in a narrow-source HIV-1 outbreak among Chinese former plasma donors
Sophie M. Andrews, Yonghong Zhang, Tao Dong, Sarah L. Rowland-Jones, Sunetra Gupta, Joakim ESBJÖRNSSON
bioRxiv 167510; doi: https://doi.org/10.1101/167510
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Distinct antibody-mediated selection in a narrow-source HIV-1 outbreak among Chinese former plasma donors
Sophie M. Andrews, Yonghong Zhang, Tao Dong, Sarah L. Rowland-Jones, Sunetra Gupta, Joakim ESBJÖRNSSON
bioRxiv 167510; doi: https://doi.org/10.1101/167510

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