Diversity of the human immunodeficiency virus type 1 (HIV-1) env sequence after vertical transmission in mother-child pairs infected with HIV-1 subtype A

Abstract

Although several virologic and immunologic factors associated with an increased risk of perinatal human immunodeficiency virus type 1 (HIV-1) transmission have been described, the mechanism of mother-to-child transmission is still unclear. More specifically, the question of whether selective pressures influence the transmission remains unanswered. The aim of this study was to assess the genetic diversity of the transmitted virus after in utero transmission and after peripartum transmission and to compare the viral heterogeneity in the child with the viral heterogeneity in the mother. To allow a very accurate characterization of the viral heterogeneity in a single sample, limiting-dilution sequencing of a 1016-bp fragment of the env gene was performed. Thirteen children were tested, including 6 with in utero infections and 7 with peripartum infections. Samples were taken the day after birth and at the ages of 6 and 14 weeks. A homogeneous virus population was seen in six (46.2%) infants, of whom two were infected in utero and four were infected peripartum. A more heterogeneous virus population was detected in seven infants (53.8%), four infected in utero and three infected peripartum. The phylogenetic trees of the mother-child pairs presented a whole range of different tree topologies and showed infection of the child by one or more maternal variants. In conclusion, after HIV-1 transmission from mother to child a heterogeneous virus population was detected in approximately one-half of the children examined. Heterogeneous virus populations were found after peripartum infection as well as after in utero infection. Phylogenetic tree topologies argue against selection processes as the major mechanism driving mother-to-child transmission but support the hypothesis that virus variability is mainly driven by the inoculum level and/or exposure time.

FIG. 1.

Rooted neighbor-joining trees of HIV-1 env (V1 to V4) DNA nucleotide sequences for the six mother-child pairs with a low intrapatient genetic distance in the children. Bootstrap values are expressed as percentages per 1,000 replicates. Only bootstrap proportions higher than 70% are indicated. □, one maternal sequence; ▪, one child sequence isolated at birth; ▴, one child sequence isolated at 6 weeks; +, one child sequence isolated at 14 weeks.

FIG. 2.

Rooted neighbor-joining trees of HIV-1 env (V1 to V4) DNA nucleotide sequences for the seven mother-child pairs with substantial intrapatient genetic distances in the children. Bootstrap values are expressed as percentages per 1,000 replicates. Only bootstrap proportions higher than 70% are indicated. □, one maternal sequence; ▪, one child sequence isolated at birth; ▴, one child sequence isolated at 6 weeks; +, one child sequence isolated at 14 weeks.

FIG. 2.

Rooted neighbor-joining trees of HIV-1 env (V1 to V4) DNA nucleotide sequences for the seven mother-child pairs with substantial intrapatient genetic distances in the children. Bootstrap values are expressed as percentages per 1,000 replicates. Only bootstrap proportions higher than 70% are indicated. □, one maternal sequence; ▪, one child sequence isolated at birth; ▴, one child sequence isolated at 6 weeks; +, one child sequence isolated at 14 weeks.