TY - JOUR
T1 - Infection of stationary human brain aggregates with HIV-1SF162 and IIIB results in transient neuronal damage and neurotoxicity
AU - Trillos-Pazos, G
AU - Kandanearatchi, A
AU - Eyeson, J
AU - King, D
AU - Vyakarnam, A
AU - Everall, I P
PY - 2004/4
Y1 - 2004/4
N2 - 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 size with a mixed cellular composition of 36% neurones, 27% astrocytes, 2%, macrophages/microglia and 14% oligodendrocytcs. Infection of SHBAs 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 hi 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.
AB - 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 size with a mixed cellular composition of 36% neurones, 27% astrocytes, 2%, macrophages/microglia and 14% oligodendrocytcs. Infection of SHBAs 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 hi 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.
UR - http://www.scopus.com/inward/record.url?scp=1942438052&partnerID=8YFLogxK
U2 - 10.1046/j.0305-1846.2003.00519.x
DO - 10.1046/j.0305-1846.2003.00519.x
M3 - Article
VL - 30
SP - 136
EP - 147
JO - Neuropathology and Applied Neurobiology
JF - Neuropathology and Applied Neurobiology
IS - 2
ER -
