Sequences in Glycoprotein gp41, the CD4 Binding Site, and the V2 Domain Regulate Sensitivity and Resistance of HIV-1 to Broadly Neutralizing Antibodies

摘要: The swarm of quasispecies that evolves in each HIV-1-infected individual represents a source closely related Env protein variants can be used to explore various aspects HIV-1 biology. In this study, we made use these identify mutations confer sensitivity and resistance the broadly neutralizing antibodies found sera selected individuals. For studies, libraries proteins were cloned from infected subjects screened for infectivity neutralization sensitivity. nucleotide sequences then compared pairs neutralization-sensitive -resistant viruses. vitro mutagenesis was specific amino acids responsible phenotype. All altering sensitivity/resistance appeared induce conformational changes simultaneously enhanced exposure two or more epitopes located different regions gp160. These occur at unique positions required maintain quaternary structure gp160 trimer, as well masking targeted by antibodies. Our results show gp41, CD4 binding site, V2 domain all have ability act global regulators also suggest assays designed support development vaccines therapeutics targeting should consider virus variation within individuals between