Significant genetic and antigenic variability within the env gene of systemic human immunodeficiency virus type 1 group O populations during the natural course of a heterosexual infection: a pilot study

Abstract

We assessed the genetic and the antigenic variability within the env gene of peripheral blood human immunodeficiency virus (HIV) type 1 (HIV-1) group O populations during the natural course of a female heterosexual infection. Our data revealed the existence of a significant increase in amino acid sequence variability within the C2-V3 and gp41 regions (P = 0.023 and P < 0.001, respectively) in association with substitutions within neutralizing epitope sequences usually selected for HIV serological assays. These antigenic variations might significantly decrease the sensitivity of classical HIV enzyme-linked immunosorbent assays with blood samples of subjects heterosexually infected by HIV-1 group O strains. These findings may be of significant use both to devise diagnostic tools and to pursue suitable therapeutic modalities in cases of heterosexual infection by outlier HIV-1 strains.

FIG. 1.

Intersample nucleotide and amino acid distances and amino acid sequences in the gp120 C2-V3 and gp41 immunodominant regions of systemic HIV-1 group O variant populations during the natural course of a heterosexual infection. (A) Graphical representation of the average distances of virus sequences from each of the four peripheral blood samples taken during the follow-up study, i.e., between 12 and 96 months after the time of heterosexual infection. Distances were calculated by taking into account the C2V3 or gp41 nucleotide alignment and the derived amino acid sequences from the C2V3 or gp41 regions. Pairwise distances among nucleotide sequences and amino acid pairwise distances were estimated by using the MEGA 3.1 program (8). The average distance between the sequences from each time point was calculated by comparison to the initial C2V3 or gp41 sequences (GenBank accession numbers X84327 and X84328, respectively) and corresponds to the estimated genetic divergence of the two viral env regions. (B) Alignments of amino acid sequences in the gp120 V3 loop and the gp41 immunodominant regions of the systemic HIV-1 variant populations between 12 and 96 months after the time of heterosexual infection. a, after subcloning and sequencing of the PCR products; for the numbers under the number of clones, the numerator represents the number of molecular clones containing identical amino acid sequences and the denominator represents the total number of sequenced molecular clones; b, initial reference sequences of the peripheral blood strain initially published by Cohen et al. (First HIV-O Symp., 1995). This sequence represented the origin reference for the present study; the gp120 amino acids in boldface correspond to the tip of the V3 loop (cysteine residues are labeled by an asterisk to define the limits of the V3 loop), whereas the gp41 sequences in boldface correspond to a major immunodominant peptide previously described (3); c, months postinfection (p.i.), corresponding to the months after the time of suspected heterosexual transmission (considered the minimal time [15 days] before the documented classical clinical signs of HIV primary infection).