Infection of stationary human brain aggregates with HIV-1 SF162 and IIIB results in transient neuronal damage and neurotoxicity
| Autor: | Annapurna Vyakarnam, Ian P. Everall, J. Eyeson, G. Trillo-Pazos, Apsara Kandanearatchi, Deborah King |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Pathology
medicine.medical_specialty Histology Microglia medicine.diagnostic_test Central nervous system Neurotoxicity virus diseases Human brain Biology medicine.disease Virology Virus Pathology and Forensic Medicine Flow cytometry Chemokine receptor medicine.anatomical_structure Neurology Physiology (medical) medicine Neurology (clinical) Progenitor cell |
| Zdroj: | Neuropathology and Applied Neurobiology. 30:136-147 |
| ISSN: | 0305-1846 |
| DOI: | 10.1046/j.0305-1846.2003.00519.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text