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An efficiently cleaved HIV-1 clade C Env selectively binds to neutralizing antibodies.
- Source :
-
PloS one [PLoS One] 2015 Mar 30; Vol. 10 (3), pp. e0122443. Date of Electronic Publication: 2015 Mar 30 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- AIDS Vaccines immunology
CD4 Antigens chemistry
CD4 Antigens pharmacology
Codon genetics
Epitopes immunology
HEK293 Cells
HIV Envelope Protein gp120 metabolism
Humans
Mutation
Protein Conformation
Solubility
env Gene Products, Human Immunodeficiency Virus chemistry
env Gene Products, Human Immunodeficiency Virus genetics
Antibodies, Neutralizing immunology
Antibody Specificity
HIV-1 immunology
Proteolysis
env Gene Products, Human Immunodeficiency Virus immunology
env Gene Products, Human Immunodeficiency Virus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25822521
- Full Text :
- https://doi.org/10.1371/journal.pone.0122443