Detection of the human immunodeficiency virus regulatory protein tat in CNS tissues.
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.
Hudson
L
L
Department of Neuropathology, Institute of Psychiatry, DeCrespigny Park, London SE5 8AF, UK.
Liu
J
J
Nath
A
A
Jones
M
M
Raghavan
R
R
Narayan
O
O
Male
D
D
Everall
I
I
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D018792:Encephalitis, Viral / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry* / Q000473:pathology / Q000821:virology; D015686:Gene Products, env / Q000032:analysis; D015696:Gene Products, tat / Q000032:analysis*; D016346:Gene Products, vif / Q000032:analysis; D015756:Genes, tat; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000032:analysis*; D012367:RNA, Viral / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D015696:Gene Products, tat; D016346:Gene Products, vif; D012333:RNA, Messenger; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus