An efficiently cleaved HIV-1 clade C Env selectively binds to neutralizing antibodies

PLoS One. 2015 Mar 30;10(3):e0122443. doi: 10.1371/journal.pone.0122443. eCollection 2015.


An ideal HIV-1 Env immunogen is expected to mimic the native trimeric conformation for inducing broadly neutralizing antibody responses. The native conformation is dependent on efficient cleavage of HIV-1 Env. The clade B isolate, JRFL Env is efficiently cleaved when expressed on the cell surface. Here, for the first time, we report the identification of a native clade C Env, 4-2.J41 that is naturally and efficiently cleaved on the cell surface as confirmed by its biochemical and antigenic characteristics. In addition to binding to several conformation-dependent neutralizing antibodies, 4-2.J41 Env binds efficiently to the cleavage-dependent antibody PGT151; thus validating its native cleaved conformation. In contrast, 4-2.J41 Env occludes non-neutralizing epitopes. The cytoplasmic-tail of 4-2.J41 Env plays an important role in maintaining its conformation. Furthermore, codon optimization of 4-2.J41 Env sequence significantly increases its expression while retaining its native conformation. Since clade C of HIV-1 is the prevalent subtype, identification and characterization of this efficiently cleaved Env would provide a platform for rational immunogen design.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / immunology
  • Antibodies, Neutralizing / immunology*
  • Antibody Specificity*
  • CD4 Antigens / chemistry
  • CD4 Antigens / pharmacology
  • Codon / genetics
  • Epitopes / immunology
  • HEK293 Cells
  • HIV Envelope Protein gp120 / metabolism
  • HIV-1 / immunology*
  • Humans
  • Mutation
  • Protein Conformation
  • Proteolysis*
  • Solubility
  • env Gene Products, Human Immunodeficiency Virus / chemistry
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology*
  • env Gene Products, Human Immunodeficiency Virus / metabolism*


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • CD4 Antigens
  • Codon
  • Epitopes
  • HIV Envelope Protein gp120
  • env Gene Products, Human Immunodeficiency Virus

Grants and funding

Funds for research was provided by THSTI-IAVI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.