title: Three amino acid residues in the envelope of human immunodeficiency virus type 1 CRF07_BC regulate viral neutralization susceptibility to the human monoclonal neutralizing antibody IgG1b12.
abstract: The CD4 binding site (CD4bs) of envelope glycoprotein (Env) is an important conserved target for anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12 (b12) could recognize conformational epitopes that overlap the CD4bs of Env. Different virus strains, even derived from the same individual, showed distinct neutralization susceptibility to b12. We examined the key amino acid residues affecting b12 neutralization susceptibility using single genome amplification and pseudovirus neutralization assay. Eleven amino acid residues were identified that affect the sensitivity of Env to b12. Through site-directed mutagenesis, an amino acid substitution at position 182 in the V2 region of Env was confirmed to play a key role in regulating the b12 neutralization susceptibility. The introduction of V182L to a resistant strain enhanced its sensitivity to b12 more than twofold. Correspondingly, the introduction of L182V to a sensitive strain reduced its sensitivity to b12 more than tenfold. Amino acid substitution at positions 267 and 346 could both enhance the sensitivity to b12 more than twofold. However, no additive effect was observed when the three site mutageneses were introduced into the same strain, and the sensitivity was equivalent to the single V182L mutation. CRF07_BC is a major circulating recombinant form of HIV-1 prevalent in China. Our data may provide important information for understanding the molecular mechanism regulating the neutralization susceptibility of CRF07_BC viruses to b12 and may be helpful for a vaccine design targeting the CD4bs epitopes.
authors.affiliation: College of Life Science, Jilin University, Changchun, 130012, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Nie
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Chen
authors.forename: Weijin
authors.initials: W
authors.lastname: Huang
authors.forename: Youchun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D002681:China; D000939:Epitopes / Q000276:immunology*; D005838:Genotype; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000276:immunology; D009500:Neutralization Tests; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000596:Amino Acids; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D007074:Immunoglobulin G; D050505:Mutant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus