Resistance of HIV-1 to the broadly HIV-1-neutralizing, anti-carbohydrate antibody 2G12

The 2G12 mAb inhibits the infection of HIV-1 laboratory-adapted viruses at 50% inhibitory concentrations (IC50) ranging from 0.02 to 0.2 μg/ml when evaluated in different cell-types. However, isolates from various HIV-1 subtypes (such as clade C, D, A/E, F and group O) were not inhibited by 2G12 mAb (IC50 > 20 μg/ml). 2G12 mAb pressure in HIV-1 IIIB- and NL4.3-infected T cell cultures selected for resistant viruses containing only few (1 to 3 N-glycosylation) deletions in gp120. The 2G12-resistant viruses keep their full sensitivity to various mannose-specific lectins and other known HIV entry inhibitors. Moreover, we observed that the NL4.3-2G12-resistant virus, with the N295K mutation in gp120, became significantly more sensitive to several mannose-specific lectins. This is, to our knowledge, the first report showing that a resistant virus generated in vitro against a neutralizing mAb and containing a mutation in gp120, has increased sensitivity to another class of HIV entry inhibitors.