title: 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.
abstract: OBJECTIVE
  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.
  
  
  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 identification 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.
authors.affiliation: aDepartment of Infection and Immunity, Laboratory of Retrovirology, Luxembourg Institute of Health (LIH) bDepartment of Infectious Diseases, Centre Hospitalier Luxembourg, Luxembourg City, Luxembourg. *Andy Chevigne, Sylvie Delhalle, Carole Seguin-Devaux, and Sabrina Deroo contributed equally to the writing of this article. †Present address: Complix Luxembourg S.A., Luxembourg City, Luxembourg.
authors.forename: Andy
authors.initials: A
authors.lastname: Chevigne
authors.forename: Sylvie
authors.initials: S
authors.lastname: Delhalle
authors.forename: Manuel
authors.initials: M
authors.lastname: Counson
authors.forename: Nadia
authors.initials: N
authors.lastname: Beaupain
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Rybicki
authors.forename: Charlène
authors.initials: C
authors.lastname: Verschueren
authors.forename: Thérèse
authors.initials: T
authors.lastname: Staub
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Schmit
authors.forename: Carole
authors.initials: C
authors.lastname: Seguin-Devaux
authors.forename: Sabrina
authors.initials: S
authors.lastname: Deroo
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D009500:Neutralization Tests; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000737:chemistry; D019718:Receptors, CXCR4 / Q000737:chemistry; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D057134:Antibodies, Neutralizing; C584933:CCR5 protein, human; C527276:CXCR4 protein, human; D022801:Complementarity Determining Regions; D015483:HIV Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019151:Peptide Library; D010455:Peptides; D019713:Receptors, CCR5; D019718:Receptors, CXCR4