HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds.

TitleHIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds.
Publication TypeJournal Article
Year of Publication2016
Authorsvan den Kerkhof TLGM, de Taeye SW, Boeser-Nunnink BD, Burton DR, Kootstra NA, Schuitemaker H, Sanders RW, van Gils MJ
JournalRetrovirology
Volume13
Issue1
Pagination48
Date Published07/07/2016
ISSN1742-4690
Abstract

BACKGROUND: Current HIV-1 immunogens are unable to induce antibodies that can neutralize a broad range of HIV-1 (broadly neutralizing antibodies; bNAbs). However, such antibodies are elicited in 10-30 % of HIV-1 infected individuals, and the co-evolution of the virus and the humoral immune responses in these individuals has attracted attention, because they can provide clues for vaccine design.

RESULTS: Here we characterized the NAb responses and envelope glycoprotein evolution in an HIV-1 infected "elite neutralizer" of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who developed an unusually potent bNAb response rapidly after infection. The NAb response was dependent on the N332-glycan and viral resistance against the N332-glycan dependent bNAb PGT135 developed over time but viral escape did not occur at or near this glycan. In contrast, the virus likely escaped by increasing V1 length, with up to 21 amino acids, accompanied by the introduction of 1-3 additional glycans, as well as 2-4 additional cysteine residues within V1.

CONCLUSIONS: In the individual studied here, HIV-1 escaped from N332-glycan directed NAb responses without changing the epitope itself, but by elongating a variable loop that shields this epitope.

DOI10.1186/s12977-016-0279-4
Alternate JournalRetrovirology
PubMed ID27388013
PubMed Central IDPMC4936165
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
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