Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
Detection of the human immunodeficiency virus regulatory protein tat in CNS tissues.
J Neurovirol. 2000 Apr;6(2):145-55. Unique Identifier : AIDSLINE MED/20284036 Hudson L; Liu J; Nath A; Jones M; Raghavan R; Narayan O; Male D; Everall I; Department of Neuropathology, Institute of Psychiatry,; DeCrespigny Park, London SE5 8AF, UK.
Abstract:
Neuropathologically, human immunodeficiency virus (HIV) is associated with a range of inflammatory disorders, extensive cortical neuronal loss, and dendritic and synaptic damage. Although the mechanisms resulting in these abnormalities are still unclear, the neurotoxic effects are thought to be due in part to viral products including the tat gene product. We have previously shown that Tat when presented to neurons extracellularly interacts with neuronal cell membranes to cause neuronal excitation and toxicity in fmole amounts. To determine the role of Tat in mediating HIV encephalitis (HIVE), we detected tat mRNA and protein in tissue extracts of nine patients with HIVE and seven patients without HIVE. Despite long autopsy times and significant degradation, tat mRNA was detected in 4/9 patients with HIVE but not in any of the seven patients without dementia. Similarly, the env mRNA was also detected in 5/9 patients with HIVE but not in the patients without HIVE. However, vif mRNA was detected in both groups of patients with (5/9) or without (2/7) HIVE. Using protein extracts from the brains of the same groups of patients we were unable to detect Tat by enzyme linked immunosorbant assay (ELISA) (sensitivity of 2 ng Tat/ml of brain tissue). However, Tat could be detected immunohistochemically and in protein extracts from the brains of rhesus macaques with encephalitis due to a chimeric strain of HIV and simian immunodeficiency virus (SHIV). Our observations support the role of Tat in the neuropathogenesis of HIV and SHIV encephalitis.
Keywords: JOURNAL ARTICLE Adult Aged Animal AIDS Dementia Complex/METABOLISM/PATHOLOGY/*VIROLOGY Blotting, Western Comparative Study Encephalitis, Viral/METABOLISM/PATHOLOGY/*VIROLOGY Enzyme-Linked Immunosorbent Assay Female Frontal Lobe/*CHEMISTRY/PATHOLOGY/VIROLOGY Gene Products, env/ANALYSIS Gene Products, tat/*ANALYSIS Gene Products, vif/ANALYSIS *Genes, tat Human HIV Infections/*VIROLOGY HIV-1/*GENETICS/ISOLATION & PURIF Lung/CHEMISTRY/PATHOLOGY/VIROLOGY Macaca mulatta Male Middle Age Postmortem Changes Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger/*ANALYSIS RNA, Viral/*ANALYSIS Sensitivity and Specificity Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. SIV/GENETICS 001030
A00A1093
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Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.
