Molecular mechanisms of human immunodeficiency virus type I mother-infant transmission

Abstract

Maternal-fetal transmission accounts for approximately 80% of all HIV-1 infections in children. Mother-to-infant transmission of HIV-1 predominately occurs perinatally at an estimated rate of more than 30%. However, the rate of transmission also depends on the symptoms of the disease and the frequency of delivery at estimated rates of 24% in symptom-free mothers and 65% in mothers with the disease or who have had a previous child with AIDS. In contrast, the rate of HIV-2 mother-infant transmission is much lower compared to HIV-1 and dually infected mothers could transmit both viruses, but the transmission of HIV-1 has generally been observed. There are no clearly defined factors, viral or host, associated with maternal transmission of HIV-1. However, maternal parameters, including advanced clinical stages of the mother, low CD4+ lymphocyte counts, maternal immune response to HIV-1, recent infection, high level of circulating HIV-1, and maternal disease progression have been implicated in an increased risk of mother-to-infant transmission of HIV-1. Molecular and biological properties of HIV-1 involved in mother-to-infant transmission are critical determinants of perinatal transmission. Studies from my laboratory compared the HIV-1 DNA sequences in the V3 region of the envelope gene from seven mother-infant pairs, following perinatal transmission. The minor HIV-1 genotype predominates initially as a homogeneous population in the infant and then becomes diverse as the infant grows older. Nucleotide sequencing directly derived from HIV-1 DNA isolated from infected mother-infant pairs' peripheral blood mononuclear cells (PBMC), alignment of deduced amino acid sequences, and phylogenetic analysis have provided a powerful tool to analyze and identify HIV-1 genotypes transmitted from mother to infant.