HIV Infection of Neural Cells

The type 1 human immunodeficiency virus (HIV-1 ), the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS), has been implicated in AIDSassociated en~ephalopathy.’,~.’,~ The pathogenesis of this encephalopathy is unclear. Results from in situ hybridization with genomic probes suggest that cells of the macrophage/microglial lineage actively produce HIV within the central nervous system.9.14 However, a number of investigators have also identified glial and endothelial cells as HIV-infected, using both in situ hybridization and antigen detection techniques.” Using a cell culture model, we have attempted to define the nature of the HIV neural cell infection in terms of entry pathway, latency, and induction of viral replication. Several cell lines and primary cell cultures representing distinct cell types of central nervous system (CNS) origin, namely, choroid plexus, gliomas, and medulloblastomas (MED) were infected with HIV-lIIIB (TABLE 1). To assess whether a specific cell type or cell surface molecule was associated with infection, we screened cells of different origin that expressed a variety of internal and surface markers. Characteristics including the cell-surface expression of histocompatibility antigens or the expression of lymphoid antigens like CD4 could not be correlated with HIV-1 infectability. Characteristics defining neural cell types, like the presence of glial fibrillary acidic protein or neurofilament proteins, also showed no correlation with infectability . As TABLE 1 indicates, both “neuronal”, and “glial” cells were infectable, and choroid plexus fibroblasts were also capable of harboring virus which could be rescued. All infectable CNS-derived cells used, except MED 341, produced latent viral infections detectable only by cocultivation with an indicator, CD4-positive cell line, SUP-