- Sharma UK,
- Trujillo J,
- Song H-F,
- et al.
Purpose of the Study
The factors controlling human immunodeficiency virus (HIV) transmission from mother to infant are not clearly defined. Maternal viral load, disease stage, and immune status have all shown an effect on transmission, yet no analysis of maternal factors fully explains why approximately 75% of children born to infected mothers escape infection. Indirect evidence suggests the existence of placental protective mechanisms that inhibit viral replication in utero. This investigation was to characterize the antiviral activity of a placental factor present in the supernatant from cultured placental stromal cells, which protected HIV-infected peripheral blood cells from virus-induced death.
First trimester chorionic villus biopsy samples from HIV-seronegative subjects were used as a source of placental stromal cells. These cells were cultured and culture supernatants were obtained. This supernatant was used to assay for antiviral activity and to examine the physical chemical and immunochemical characterization of the placental factor.
The inhibitory activity present in the supernatant was not attributable to the presence of any known cytokine previously reported to have anti-HIV effects. The placental factor had no specific suppressive effect on the infectivity of cell-free HIV, and envelope-mediated membrane fusion appeared to be uninfected. However, infected peripheral blood mononuclear cells treated with placental factor revealed reduced expression of all viral proteins and the production of virions with 10- to 100-fold reduced infectivity.
The placental factor described is a small, heat and pH stable molecule with broad suppressive activity against different strains of HIV. The factor does not share identity with any known cytokines. This factor could play an important role in the protection of the fetus and newborn from HIV infection and further studies to purify and characterize this factor are in progress.
How so many infants escape HIV infection in utero has remained a mystery. It is generally presumed now that most perinatal infections occur peripartum rather than during early and midgestation. This supports the author's claim that some feature of placental physiology impacts the transmission of HIV to the developing fetus. Further, active infection is not prevented by this factor, although direct cytopathology and individual virion infectivity is decreased. If this factor can be isolated and characterized, it may provide the basis for the development of a new class of HIV interventions.