Characteristics of HIV-1 gp120 env sequences in mother-child pairs infected with HIV-1 subtype CRF01_AE

Background

Previous studies have suggested that mother-to-child transmission of HIV-1 is often characterized by acquisition of a homogeneous viral quasispecies in the infant [1–3], suggestive of a genetic bottleneck. In this study, we have analyzed the molecular characteristics of transmitted HIV-1 viruses in a homogeneous population infected by CRF01_AE variants in Thailand.

Materials and methods

Seventeen mother-child pairs were studied. The infants were not breastfed. Six infants were infected in utero and 11 infants were infected intrapartum. The env sequences covering the entire gp120 were amplified from both the proviral DNA of maternal PBMC collected at delivery and the plasma viral RNA at first positive time point of infants. The amplified products were cloned and sequenced. A total of 353 clones were available for analysis.

Results

Phylogenetic analysis indicated 2 patterns of transmission: 14 mothers transmitted a single variant and 3 mothers transmitted multiple variants to their infants. The mean genetic distance of viruses from the mothers was significantly higher than those from the infants (2.7% vs. 0.6%; P<0.01), but without any difference according to timing of transmission, either in utero or intrapartum. The length of gp120 and number of potential N-linked glycosylation sites (PNGS) were similar in both the entire gp120 and individual regions of gp120 of all mother-child pairs. However, our data indicate that 4 PNGS positions (N241, N301, N354, and N384) that appeared conserved in all infant variants but were irregularly present in the mothers might be associated to a selective advantage. In addition, we report the first case to our knowledge of transmission to an infant of a recombinant virus issued from variants from his mother.

Conclusions

Our results provide additional evidence that despite a complex viral population in the mother, only viruses of a restricted subset are transmitted to the infant, independently of the timing of transmission, in utero or intrapartum. We did not find that shorter gp120 or fewer PNGS were characteristics of viruses transmitted from mother to infant, as it was suggested for sexually transmitted viruses at least for a few subtypes [4–7]. Four PNGS were selected for transmitted viruses, supporting the role of the “glycan shield” of the HIV-1 envelope in conferring a selective advantage.