Human immunodeficiency virus type 1 in spinal cords of acquired immunodeficiency syndrome patients with myelopathy: expression and replication in macrophages

Abstract

Spinal cord disease is common in patients infected with human immunodeficiency virus type 1 (HIV-1), and a characteristic vacuolar myelopathy is present at autopsy in approximately one-fourth of acquired immunodeficiency syndrome patients. Pathologic examination of the spinal cord shows vacuolation of white matter and infiltration by macrophages, a process distinct from HIV-1 encephalopathy. To determine the presence and localization of HIV-1 RNA in the spinal cords of acquired immunodeficiency syndrome patients with vacuolar myelopathy, we used the technique of combined in situ hybridization and immunohistochemical staining on the same slide. Spinal cord tissue sections were stained with markers for macrophages, endothelial cells, oligodendroglia, astrocytes, and myelin and then hybridized in situ with HIV-1-specific RNA probes. Combined in situ hybridization and immunohistochemical staining on three spinal cords showed HIV-1 expression in mononuclear and multinucleated macrophages localized mainly to areas of myelopathy in spinal cord white matter. Immunohistochemical staining and electron microscopy showed myelin within macrophages and electron microscopy revealed HIV-1 budding from macrophages. These data suggest a role for HIV-1-infected macrophages locally in the pathogenesis of vacuolar myelopathy and add to the body of evidence that these cells play a role systemically in the development of HIV-1-related disease.