Molecular and biological characterization of human immunodeficiency virus type 1 envelope gp120 associated with maternal-fetal transmission

Abstract

Vertical transmission of HIV-1 represents a major, global health concern with particular regard to developing areas of the world, and perinatally acquired infections account for the majority of all pediatric HIV-1 cases. Maternal-fetal transmission of HIV-1 occurs at three stages: prepartum, intrapartum, and post-partum, however the mechanism of this transmission is not yet clearly defined. Additionally, the rate of transmission is estimated at ∼30%, leaving ∼70% of infected mothers who do not transmit to their infants. While several maternal factors including viral load, clinical stage of the mother, low CD4 counts, recent infection, and the maternal immune response to infection have been implicated in transmission, the viral factors which may influence transmission are not known. In this study, we have investigated the molecular and biological properties associated with the env V3 region and the entire env from both transmitting and non-transmitting mothers. Our results show that the minor genotypes of the mothers' heterogeneous viral populations are transmitted to their infants, the biological properties associated with the transmitted variants' V3 regions appear to be macrophage tropic (R5) and non-syncytium inducing, and the transmitted variants are initially maintained in the infants with the same properties. In addition, the molecular analyses of the env of non-transmitting mothers, including the variable regions V1-V2, V3, and V4-V5 were found to be significantly more homogeneous than that of transmitting mothers, suggesting that a limited heterogeneity within an infected mother may prevent vertical transmission. Since effective therapies should target the specific properties of transmitted variants, these results provide significant insight into the molecular mechanisms of maternal-fetal transmission, aiding the development of effective therapies for prevention of transmission and treatment of disease.