- Poster presentation
- Open Access
Mutations in the V1 domain of Thai CRF01-AE viruses that confer sensitivity/resistance to broadly neutralizing antibodies
© O'Rourke et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Clinical Trial
- Infectious Disease
- Cancer Research
- Structural Study
- Infected Individual
Antibodies to the V1/V2 domain of gp120 have recently been identified as a correlate of protection in the RV144 clinical trial. To better understand the specificity of broadly neutralizing antibodies) to the V1/V2 domain of Thai CRF01_AE viruses, we analyzed the specificity of antibodies in HIV+ elite neutralizer (EN) sera by swarm analysis.
Swarm analysis makes use of the swarm of closely envelope variants that evolve in each HIV-1 infected individual, as a source of naturally occurring and biologically relevant mutations that confer neutralization sensitivity/resistance. Envelopes from clade B and CRF01_AE viruses were tested for neutralization sensitivity/resistance with sera from ENs infected with clade B and CRF01_AE viruses.
We found five mutations in the V1 domain that affected neutralization sensitivity/ resistance of CRF01_AE viruses. This differed from clade B viruses in which mutations altering neutralization sensitivity/resistance clustered in the V2 domain. Structural studies have shown that the V1/V2 domain of gp120 consists of a four-stranded β-sheet structure. We found that mutations affecting neutralization sensitivity/resistance in Thai CRF01_AE viruses clustered around the exposed turn at the junction of the A-B strands. In contrast, the mutations that altered neutralization sensitivity/resistance in clade B viruses clustered around exposed turns at the junction of the B-C and the C-D strands.
The present studies suggest that there is a major difference in the antigenic structure of the V1V2 domain between clade B and CRF01_AE envelope proteins. These results suggest that antibodies to the V1 domain of CRF01_AE envelope proteins should be evaluated as a correlate of protection in the RV144 trial. For this purpose, studies using novel proteins and scaffolds, that replicate the structure of conformation- and glycoform- dependent epitopes in the V1/V2 domain, are under investigation.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.