HIV-1 infection of primary human neuroblasts

Abstract

Central nervous system (CNS) disorders are frequent in HIV-1-infected individuals, particularly in newborns and children, and are accompanied by histological alterations resulting in neuronal loss. Although several tumor-derived neuroectodermal cell lines can be infected by HIV-1, it has been reported that primary neural cells cannot be infected after they differentiate. However, pediatric AIDS is often the result of HIV-1 infection occurring during fetal development and early postnatal life, when neural cells are not yet differentiated. Here we show that primary cell cultures derived from the human fetal olfactory system which are representative of the developing CNS can be infected by both HIV-1 strains, the monocyte-macrophagotropic BaL and the lymphotropic HTLV-IIIB, although they do not express the CD4 molecule. In addition, the levels of viral replication are higher with the HIV-1 BaL than with the IIIB isolate. These results suggest that (1) during development immature neurons are susceptible to HIV-1 infection; (2) monocyte-macrophagotropic HIV-1 strains may preferentially be involved in the productive infection of the nervous system; and (3) a mechanism(s) other than the CD4-mediated viral entry is responsible for HIV-1 infection of immature neurons.