Restricted genetic diversity of HIV-1 subtype

Prevention of Mother-To- Child Transmission

Restricted genetic diversity of HIV-1 subtype C envelope glycoprotein from perinatally infected

Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, the authors analyzed the viral env quasispecies of six mother-infant transmission pairs and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission. The V1-V5 region of env was amplified from 6 mother-infant transmission pairs baseline samples and 334 DNA sequences in total were analyzed. A comparison of the viral population derived from the mother and infant revealed a severe genetic bottleneck occurring during perinatal transmission, which was characterized by low sequence diversity in the infant. Phylogenetic analysis indicates that most likely in all their infant subjects a single founder virus was responsible for establishing infection. Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses. In addition, a similar intensity of selection was seen between mothers and infants with a higher rate of synonymous (dS) compared to nonsynonymous (dN) substitutions evident (dN/dS<1).>strong genetic bottleneck occurs during perinatal transmission of HIV-1 subtype C. This is evident through population diversity and phylogenetic patterns where a single viral variant appears to be responsible for infection in the infants. As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope. This suggests that viruses with the restricted glycosylation in envelope glycoprotein appeared to be preferentially transmitted during HIV-1 subtype C perinatal transmission. In addition, their findings also indicated that purifying selection appears to predominate in shaping the early intrahost evolution of HIV-1 subtype C envelope sequences.

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Editor’s note: All six infants in this study were negative for HIV at birth by PCR (polymerase chain reaction) and viral isolation, suggesting that transmission occurred during delivery or breastfeeding. They all had passively acquired maternal antibody, which may have imposed a selection pressure on the transmitted virus. The low amount of maternal virus they were exposed to through breastfeeding may also have contributed to the genetic bottleneck documented here. Although the mothers had a variety of viral quasispecies, only a single founder virus was transmitted. However, that virus had low sequence diversity, restricted glycosylation in the Env V1-V5 region, and a higher replicative fitness suggesting that it was better able to establish efficient replication in its new host. Four of these infants were fast progressors, dying before the age of 1 year. Studies such as this one characterising newly transmitted or founder viruses can help inform new interventions to prevent mother-to-child transmission.