title: Efficiency of neutralizing antibodies targeting the CD4-binding site: influence of conformational masking by the V2 loop in R5-tropic clade C simian-human immunodeficiency virus.
abstract: In R5-tropic clade C simian-human immunodeficiency viruses (SHIV-Cs), we identified a 3-asparagine (3N) deletion mutation in the V2 loop stem of gp120 as the major determinant of neutralization escape of the anti-CD4-binding site (anti-CD4-bs) neutralizing monoclonal antibody (nMAb) b12. However, the more potent anti-CD4-bs nMAbs VRC01 and VRC03 were not sensitive to this mutation. Using isogenic tier 1 or tier 2 proviruses differing only in the 3N mutation, we showed that this mutation might result in selective conformational b12 epitope masking. Therefore, human immunodeficiency virus (HIV) Env immunogens targeting the CD4-bs and designed to neutralize tier 2 viruses should take conformational masking by the V2 loop into account.
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Watkins
authors.forename: Juan
authors.initials: J
authors.lastname: Diaz-Rodriguez
authors.forename: Nagadenahalli B
authors.initials: NB
authors.lastname: Siddappa
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D014771:Virion; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus