Genetic diversity of primary HIV-1 isolates and their sensitivity to antibody-mediated neutralization

Wide differences exist among primary isolates of HIV-1 in their sensitivity to antibody-mediated neutralization. While it is well documented that even short-term tissue culture amplification of HIV-1 leads to a reduction in the genetic diversity of the viral quasispecies seen in vivo, viral isolates, while relatively homogeneous, are generally not clonal. We investigated whether the extent of genetic diversity within primary viral isolates correlates with their general susceptibility to neutralization. We compared the number of V1V2 and V3-V5 envelope variants detectable within 16 primary isolates selected to represent the extremes of the neutralization sensitive and resistant phenotypes. Using DNA heteroduplex tracking assays to estimate the extent of genetic diversity in these two regions of the envelope locus, we found that these primary isolates were made up of one to five distinguishable V1V2 and V3-V5 sequence variants. We found that higher levels of env genetic diversity did not correlate with increased resistance to antibody neutralization.