Investigation of the reversion of HXB2thr582 neutralization-resistant variant of HIV-1

A spontaneous revertant of the immune selected variant, HXB2thr582, was observed in vitro following its long term culture in the absence of immune selecting serum. In order to determine the molecular basis for the reversion to the parental phenotype of neutralization sensitivity, a 900 base pair region of the envelope gene was amplified by polymerase chain reaction and sequenced. Reversion was shown to be due to a simple back mutation, resulting in the parental genotype and an alanine residue instead of a threonine residue at position 582. The 582 region within the transmembrane protein is highly conserved. It has been observed earlier that minimal amino acid substitution in this portion of HIV-1 envelope can lead to lack of infectivity. The spontaneous reversion to parental genotype of HXB2thr582 variant further suggests that the 582 region possesses a functional significance which remains to be elucidated.