Infection of stationary human brain aggregates with HIV-1 SF162 and IIIB results in transient neuronal damage and neurotoxicity.
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 mm(3) 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.
Trillo-Pazos
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Section of Experimental Neuropathology and Psychiatry, Institute of Psychiatry, King's College London, DeCrespigny Park, London SE5 8AF, UK.
Kandanearatchi
A
A
Eyeson
J
J
King
D
D
Vyakarnam
A
A
Everall
I P
IP
D001921:Brain / Q000473:pathology / Q000821:virology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005333:Fetus; D005434:Flow Cytometry; D005911:Gliosis / Q000821:virology; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000473:pathology* / Q000821:virology; D009836:Oligodendroglia / Q000473:pathology / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism
D016655:HIV Core Protein p24; D019713:Receptors, CCR5