HIV‐1 infection of subcortical astrocytes in the pediatric central nervous system

TLDR

Early pediatric HIV‑1 neuropathology reports identified viral particles in astrocytes, but recent studies indicate that proviral antigen expression in infected astrocytes falls below conventional detection limits. The study examined autopsy tissue from 12 infants and children with AIDS‑associated encephalopathy to detect HIV‑1‑infected astrocytes using combined isotopic in situ hybridization and astrocyte immunohistochemistry. Detection relied on highly sensitive radiolabeled DNA/RNA probes for in situ hybridization of viral nucleic acids, coupled with immunohistochemistry to identify astrocytes. HIV‑1 nucleic acids were found in subcortical astrocytes of four children with leukoencephalitis, and Nef protein was detected in astrocytes of two, indicating a persistent, non‑productive infection and suggesting subcortical astrocytes as an unrecognized reservoir.

Abstract

Early reports of pediatric HIV-1-associated neuropathology described the presence of viral particles in some astrocytes, implicating direct infection of the immature nervous system as a contributing factor to the observed neuropathology. Several recent reports suggest that in those astrocytes infected with HIV-1, the level of antigenic expression of the proviral genome is below the sensitivity limits of conventional histochemical techniques. Identification of these astrocytes would instead require the use of a highly sensitive radiolabeled DNA or RNA probe for in situ hybridization to detect the persistent viral nucleic acids. To test this hypothesis, we examined autopsy tissue from 12 infants and children with AIDS-associated encephalopathy for the presence of HIV-1-infected astrocytes using combined isotopic in situ hybridization for the detection of viral-specific nucleic acids and immunohistochemistry for the identification of astrocytes. We detected HIV-1 nucleic acids in astrocytes in subcortical white matter from four pediatric patients with moderate to extensive leukoencephalitis. While gp41 was detectable only on macrophages and multinucleated giant cells, HIV-1 Nef protein was present in cells morphologically identified as astrocytes in two of these patients, further suggesting that HIV-1 establishes a persistent rather than a productive infection in astrocytes. Subcortical astrocytes may therefore be an unrecognized reservoir for HIV-1 in the developing nervous system of some children with AIDS-associated leukoencephalitis.