P09-04. Charge changes in the alpha2-helix in the C3 region of the HIV-1 subtype C envelope mediate neutralization escape

Results Escape in CAP88 was mediated by 2 of 3 amino acid changes in the alpha2-helix by 6 months post-infection An I339N mutation resulted in the formation of a predicted N-linked glycan (PNG) suggesting possible glycan shielding. Sequences also contained either an E343K or an E350K substitution resulting in charge switches from negative to positive residues. Modeling of these non-contiguous changes onto helical wheel diagrams showed both residues were in close physical proximity to I339N. In CAP177, neutralization escape was not associated with changes in the number of PNGs. Three of the 5 changes observed, E337K, Q344K and E351K all lay on the same face of the alpha2-helix. However all 5 substitutions were charge changes from neutral or negatively-charged residues to positively-charged residues. In CAP206, two of the three changes observed in escaped clones (though mutagenesis data was not available) were substitutions also resulting in positive charges, G348R and N351K.