Isolation of an HIV-1 neutralizing peptide mimicking the CXCR4 and CCR5 surface from the heavy-chain complementary determining region 3 repertoire of a viremic controller

Andy Chevigne*, Sylvie Delhalle, Manuel Counson, Nadia Beaupain, Arkadiusz Rybicki, Charlene Verschueren, Therese Staub, Jean Claude Schmit, Carole Seguin-Devaux, Sabrina Deroo

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Objectives: The recent identification of neutralizing antibodies able to prevent viral rebound reemphasized the interest in humoral immune responses to control HIV-1 infection. In this study, we characterized HIV-1-inhibiting sequences from heavy-chain complementary determining region 3 (HCDR3) repertoires of a viremic controller. Design and methods: IgM and IgG-derived HCDR3 repertoires of a viremic controller presenting plasma-neutralizing activity and characterized by over 20 years of infection with a stable CD4+ T-cell count were displayed on filamentous phage to identify HCDR3 repertoire-derived peptides inhibiting HIV-1 entry. Results: Screening of phage libraries against recombinant gp120 led to the identifi-cation of an HCDR3-derived peptide sequence (LRTV-1) displaying antiviral properties against both X4 and R5 viruses. The interaction of LRTV-1 with gp120 was enhanced upon CD4 binding and sequence comparison revealed homology between LRTV-1 and the second extracellular loop of C-X-C chemokine receptor type 4 (CXCR4) (11/23) and the N-terminus of C-C chemokine receptor type 5 (CCR5) (7/23). Alanine scanning experiments identified different clusters of residues critical for interaction with the viral envelope protein. Conclusions: LRTV-1 peptide is to date the smallest human HCDR3 repertoire-derived peptide identified by phage display inhibiting HIV entry of R5 and X4 viruses. This peptide recognizes a CD4-dependent gp120 epitope critical for coreceptor binding and mimics the surface of CXCR4 and CCR5. Our data emphasize the potential of human HCDR3 immune repertoires as sources of small biologically active peptides for HIV cure.

Original languageEnglish
Pages (from-to)377-382
Number of pages6
JournalAIDS
Volume30
Issue number3
DOIs
Publication statusPublished - 28 Jan 2016

Keywords

  • CCR5
  • CXCR4
  • HIV-1
  • Heavy-chain complementary determining region 3
  • Neutralizing antibody
  • Phage display
  • Viremic controller

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