Background:  The likelihood for perinatally acquired infection with HIV-1 is strongly associated with maternal viral load. However, we and others have observed infants born to drug-naïve women with high viral load, but not infected, and, conversely, infants born to women with low viral load who were infected, suggesting that maternal co-factors may have an important influence on transmission outcome. The relation of maternal co-factors to mother/infant transmission outcome is largely unknown.

Methods:  Prior to the availability of ART intervention (1999 to 2000), we collected peripheral blood mononuclear cells (PBMC) from 20 seronegative and 25 drug-naïve HIV-1C-positive mothers in Botswana, including 14 mothers who did not transmit HIV-1C to their infants (NTR) and 11 mothers who did transmit HIV-1C (TR). The cells were then subjected to an assessment of gene expression with the use of 23,000 gene-probes to identify differentially expressed genes associated with maternal infection and transmission.

Results:  We identified highly significant sets of differentially expressed genes in PBMC that were associated with infection status and transmission outcome. Maternal HIV-1C infection was represented by increases of innate immune response genes, implicating toll-like receptor (TLR), interferon-stimulated pathways, and RNA editing genes engaged as part of a broad antiviral response in these mothers. HIV-1C RNA processing gene expression was largely reduced, with the notable exception of genes associated with antiviral RNA editing / response. NTR mothers displayed an over-representation of immune response genes when compared with TR mothers and had viral load associated increases in RNA splicing factor expression.

Conclusions:  Differential expression of genes associated with broad innate immune response, RNA processing, RNA editing, and differential splicing were associated with maternal HIV-1C infection and perinatal transmission outcome.