PLoS ONE (Jan 2015)

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

  • Saikat Boliar,
  • Supratik Das,
  • Manish Bansal,
  • Brihaspati N Shukla,
  • Shilpa Patil,
  • Tripti Shrivastava,
  • Sweety Samal,
  • Sandeep Goswami,
  • C Richter King,
  • Jayanta Bhattacharya,
  • Bimal K Chakrabarti

DOI
https://doi.org/10.1371/journal.pone.0122443
Journal volume & issue
Vol. 10, no. 3
p. e0122443

Abstract

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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.