An Efficiently Cleaved HIV-1 Clade C Env Selectively Binds to Neutralizing Antibodies

作者：Boliar Saikat; Das Supratik; Bansal Manish; Shukla Brihaspati N; Patil Shilpa; Shrivastava Tripti; Samal Sweety; Goswami Sandeep; King C Richter; Bhattacharya Jayanta; Chakrabarti Bimal K^*

来源：PLos One, 2015, 10(3): e0122443.

DOI：10.1371/journal.pone.0122443

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.

• 出版日期2015-3-30