Infection of stationary human brain aggregates with HIV‐1 SF162 and IIIB results in transient neuronal damage and neurotoxicity

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Abstract
The cellular basis of HIV associated dementia has been correlated with microglial activation and neuronal dysfunction in symptomatic HIV‐1 disease. As a cellular model of HIV‐1 infection of brain tissue in vitro, we established a stationary human brain aggregate (SHBA) system to compare infection of HIV‐1 SF162 (R5 virus) to that of IIIB (X4 virus). Aggregates were analysed by immunohistochemistry, morphometry, flow cytometry and p24 ELISA. SHBAs had a 1 mm3 size with a mixed cellular composition of 36% neurones, 27% astrocytes, 2% macrophages/microglia and 14% oligodendrocytes. Infection of SHBA's with the R5 HIV‐1 SF162 virus led to the expression of HIV‐1 p24 antigen in 6% of cells. Infection with this R5 using virus culminated in transient neuronal damage and a decrease in mitotically active progenitor cells within aggregates. Infection with X4 using HIV‐1 IIIB was associated with astrocytosis and neurotoxicity. We propose that: (1) the pattern of cellular damage elicited by HIV‐1 infection of brain tissue in vitro depends on virus subtype as determined by its preferential use of R5 or X4 chemokine receptors for entry into cells; (2) SHBAs are a reliable and readily established model of the cellular complexity of human brain tissue in vitro.