title: Resistance of Subtype C HIV-1 Strains to Anti-V3 Loop Antibodies.
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.
authors.affiliation: Department of Pharmacology, New York University School of Medicine (NYSoM), New York, NY 10016, USA.
authors.forename: David
authors.initials: D
authors.lastname: Almond
authors.forename: Chavdar
authors.initials: C
authors.lastname: Krachmarov
authors.forename: James
authors.initials: J
authors.lastname: Swetnam
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Timothy
authors.initials: T
authors.lastname: Cardozo