About this Journal Submit a Manuscript Table of Contents
Advances in Virology
Volume 2012 (2012), Article ID 803535, 8 pages
http://dx.doi.org/10.1155/2012/803535
Research Article

Resistance of Subtype C HIV-1 Strains to Anti-V3 Loop Antibodies

1Department of Pharmacology, New York University School of Medicine (NYSoM), New York, NY 10016, USA
2Public Health Research Institute and New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101, USA
3Department of Pathology, New York University School of Medicine (NYSoM), New York, NY 10016, USA

Received 19 October 2011; Accepted 2 January 2012

Academic Editor: Domenico Genovese

Copyright © 2012 David Almond et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

HIV-1’s subtype C V3 loop consensus sequence exhibits increased resistance to anti-V3 antibody-mediated neutralization as compared to the subtype B consensus sequence. The dynamic 3D structure of the consensus C V3 loop crown, visualized by ab initio folding, suggested that the resistance derives from structural rigidity and non-β-strand secondary protein structure in the N-terminal strand of the β-hairpin of the V3 loop crown, which is where most known anti-V3 loop antibodies bind. The observation of either rigidity or non-β-strand structure in this region correlated with observed resistance to antibody-mediated neutralization in a series of chimeric pseudovirus (psV) mutants. The results suggest the presence of an epitope-independent, neutralization-relevant structural difference in the antibody-targeted region of the V3 loop crown between subtype C and subtype B, a difference that we hypothesize may contribute to the divergent pattern of global spread between these subtypes. As antibodies to a variable loop were recently identified as an inverse correlate of risk for HIV infection, the structure-function relationships discussed in this study may have relevance to HIV vaccine research.