Analysis of HIV-1 envelope evolution suggests antibody-mediated selection of common epitopes among Chinese former plasma donors from a narrow-source outbreak

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Abstract

The HIV-1 envelope mutates rapidly to evade recognition and killing, and is a major target of humoral immune responses and vaccine development. Identification of common epitopes for vaccine development have been complicated by genetic variation on both virus and host 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 under significant positive selection in ≥50% of the study participants, and 22 sites consistent with antibody-mediated selection. Despite strong selection pressure, some sites housed a limited repertoire of amino acids. Structural modelling revealed that most of the variable amino acid sites were located on the exposed distal edge of the Gp120 trimer, whilst invariant sites clustered within the centre of the protein complex. Two sites, flanking the V3 hypervariable loop, represent novel antibody sites. Analysis of HIV-1 evolution in hosts infected with a narrow-source virus may provide insight and novel understanding of common epitopes under antibody-mediated selection. If verified in functional studies, such epitopes could be suitable as targets in vaccine development.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • University of Oxford
  • Capital University of Medical Sciences
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
Originalspråkengelska
Artikelnummer5743
TidskriftScientific Reports
Volym8
Utgivningsnummer1
StatusPublished - 2018 dec 1
PublikationskategoriForskning
Peer review utfördJa