HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29549260.
- Also identified by DOI 10.1038/s41467-018-03565-6 and PMC identifier 5856820.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide ("Man<sub>9</sub>-V3") for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage ("DH270"), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man<sub>9</sub>-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs-the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen.
Medical subject headings
- Antibodies, Neutralizing
- Gene Products, env
- HIV Antibodies
- HIV Infections
- HIV-1