Productive infection of human fetal microglia by HIV-1.

Abstract

Central nervous system disease is a frequent finding in both pediatric and adult AIDS. Microglia have been shown to be the major target of HIV-1 infection in the central nervous system. However, studies in vitro concerning susceptibility of human microglia to HIV-1 infection reported conflicting results; microglia from adult brain showed productive infection by HIV-1, whereas microglia from fetal brain did not. To investigate this further and to define the possible mechanisms responsible for this difference, we prepared highly purified human microglial cell cultures from fetuses of 16 to 24 weeks' gestation and exposed them to monocytotropic (HIV-1 JR-FL and HIV-1 JR-CSF) isolates of HIV-1. Culture supernatants were examined for the presence of p24 antigen for a 4-week period after viral exposure. Concurrently, potential cytopathic effects and cellular viral antigen expression (gp41 and p24) were examined by light microscopy in combination with immunocytochemistry. The results showed that human fetal microglia can be productively infected by HIV-1 as judged by p24 antigen capture assay, syncytia formation, and gp41 and p24 immunoreactivity of infected microglia. In addition, by electron microscopy, numerous viral particles characteristic of HIV-1 were present both in the intracellular and extracellular compartments. Uninfected cultures or astrocytes overgrown in the microglial cultures did not show evidence of infection under identical experimental conditions. These data demonstrate that human fetal microglia, like their adult counterparts, are susceptible to HIV-1 infection in vitro and can support the production of virus.