Abstract
‘Restricted’ human immunodeficiency virus type (HTV-1) infection of astrocytes is recognized in vivo in some pediatric and adult AIDS brains and in vitro in a small proportion of transfected primary fetal astrocytes. We investigated the extent of HTV-1JR-FL. expression in fetal astrocytes and macrophages cultivated alone or together. Peak HIV-1 p24 antigen titres in supernatant fluids of macrophage cultures were increased with monocyte/macrophages from certain donors and were higher when macrophages were cocultivated with astrocytes. Structural HTV-1 gene (gp 41 and pot) products (protein and mRNA) were observed only in macrophages. Ten days after HTV-1JR-FL infection, astrocytes in a monoculture were stained negative or only weakly positive (1 - 2+) for Nef, whereas in a coculture up to 100% of astrocytes displayed Nef staining (up to 4+) in the cytoplasm. The streptavidine-biotine-peroxidase technique with certain monoclonal antibodies to Nef (Ovod et al, 1992) was specific for infected astrocytes. The intensity of Nef staining was higher in astrocytes cultivated with monocyte/macrophages from certain donors. In the coculture, tumor necrosis factor-α (TNF-α) was expressed in the astrocyte cytoplasm earlier after coinfection with HIV-1 and cytomegalovirus (CMV) compared to infection with HTV-1 alone. Interleukin-6 (IL-6) was secreted spontaneously and transiently in uninfected cocultures, but in a prolonged fashion following HTV-1 and HTV-1/CMV infections. The interactions between HTV-1- and CMV-infected macrophages and astrocytes lead to upregulation of TNF-a and IL-6 and enhancement of productive HIV-1 infection of macrophages and of ‘restricted’ HTV-1 infection of astrocytes with implications for the pathogenesis of AIDS dementia.