title: Naturally occurring substitutions of conserved residues in human immunodeficiency virus type 1 variants of different clades are involved in PG9 and PG16 resistance to neutralization.
abstract: The recently described anti-human immunodeficiency virus type 1 (HIV-1) human mAb PG9 and PG16 are cross-clade broadly neutralizing. Therefore, it can be postulated that the targeted epitope(s) are highly conserved among variants of the entire group M. We analysed the sensitivity to PG9 and PG16 of pseudotyped viruses carrying envelope glycoproteins from the viral quasispecies of three HIV-1 clade CRF01_AE-infected patients. The broad heterogeneity in sensitivity to PG9 and PG16, despite closely genetically related envelope glycoproteins issued from single individuals, allowed us to identify two gp120 cross-clade conserved residues, a lysine at position 168 in the V2 loop and an isoleucine at position 215 in the C2 region, whose substitutions were associated with resistance to PG9 and PG16. By site-directed mutagenesis, we confirmed both in clades B and CRF01_AE that the substitutions K168E and I215M have a major impact on PG9 and PG16 neutralization sensitivity of pseudotyped viruses.
authors.affiliation: Université François Rabelais, Inserm U966, 10 blvd Tonnellé, 37032 Tours cedex, France.
authors.forename: Suzie
authors.initials: S
authors.lastname: Thenin
authors.affiliation: Université François Rabelais, Inserm U966, 10 blvd Tonnellé, 37032 Tours cedex, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Roch
authors.affiliation: Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.|Université François Rabelais, Inserm U966, 10 blvd Tonnellé, 37032 Tours cedex, France.
authors.forename: Tanawan
authors.initials: T
authors.lastname: Samleerat
authors.affiliation: Université François Rabelais, Inserm U1100, Tours, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Moreau
authors.affiliation: Université François Rabelais, Inserm U966, 10 blvd Tonnellé, 37032 Tours cedex, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Chaillon
authors.affiliation: Université François Rabelais, Inserm U966, 10 blvd Tonnellé, 37032 Tours cedex, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Moreau
authors.affiliation: Université François Rabelais, Inserm U966, 10 blvd Tonnellé, 37032 Tours cedex, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Barin
authors.affiliation: Université François Rabelais, Inserm U966, 10 blvd Tonnellé, 37032 Tours cedex, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Braibant
mesh_terms: D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D004252:DNA Mutational Analysis; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology; D020125:Mutation, Missense; D009500:Neutralization Tests; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D050505:Mutant Proteins; D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus