Subtle alteration of residues including N-linked glycans in V2 loop modulate HIV-1 neutralization by PG9 and PG16 monoclonal antibodies.
Recent discovery of several potent and broadly neutralizing monoclonal antibodies (MAbs) (such as PG9 and PG16) to HIV-1 provided clues on newer vaccine targets. In the present study, we found an env clone obtained from a slow progressor showing significant resistance to PG9 and PG16 MAbs in sharp contrast to other contemporaneous autologous env clones. By constructing chimeric envelopes and specific substitutions we found that both loop length and spatial orientation of glycan residues in addition to the net charge of the β sheet C region that directly binds to PG9 CDRH3 within V2 loop significantly modulated HIV-1 sensitivity to PG9 and PG16 MAbs. Similar observation were made with several other Envs which varied in length, glycan content and net charge in PG9 contacting complementary region in V2 loop. Our data indicated that subtle change within V2 loop alone modulates exposition of quaternary epitopes that are targets of PG9/PG16 MAbs.
Department of Molecular Virology, National AIDS Research Institute, Pune-411026, India.
Rajesh
R
Ringe
Sanjay
S
Phogat
Jayanta
J
Bhattacharya
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002460:Cell Line; D018604:Epitope Mapping; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D011134:Polysaccharides; D054299:env Gene Products, Human Immunodeficiency Virus