Transcription of Human Immunodeficiency Virus Promoter in CNS-Derived Cells: Effect of TAT on Expression of Viral and Cellular Genes

  • Kamel Khalili
  • J. Paul Taylor
  • Crystina Cupp
  • Michael Zeira
  • Shohreh Amini


Approximately 60% of patients with AIDS have neurologic symptoms, the so-called AIDS-related subacute encephalopathy, and more than 80% are found to have neuropathologic abnormalities at autopsy.1,2 The most common neurologic problems include: toxoplasmosis, cryptococcosis, primary lymphoma of the central nervous system (CNS), and subacute encephalitis or AIDS encephalopathy. 3–8 Histologic analysis of CNS tissues from AIDS patients shows enlargement of oligodendrocytes and formation of multinucleated giant cells.9–17 The detection of HIV DNA in the brain and recovery of infectious virus particles from cerebrospinal fluid and brain tissue of patients with AIDS have suggested that HIV-1 may be directly responsible for some of the neurologic deficits found in these patients.18–22 The presence of CD4, the high-affinity receptor for HIV-1 in human brain tissue and in certain glioma cell lines, has been reported.23,24 Furthermore, HIV 1 has been shown to infect glial cells in vitro and has been detected in oligodendrocytes and astroglial cells in vivo. 18, 23, 25–28 Together, these observations indicate that HIV-1 is not only lymphotropic but also neurotropic.However, the exact mechanisms involved in the neuropathogenesis of HIV-1 and AIDS dementia complex remain unclear. A simple model would envisage the direct infection of neurons and glia by neurotropic HIV-1 that results in indirect or direct cytotoxicity mediated by cytotoxic T cells. Alternatively, infection of monocytic macrophages with HIV-1 may lead to the release of a diffusible inflammatory component(s) that destroys neighboring neural cells, and/or results in the release of cytokines which are toxic to neural cells. Moreover, other neurotropic viruses, JCV and cytomegalovirus (CMV) may act as cofactors in the pathogenesis of AIDS-related neurologic disorders.


Glial Cell Human Immunodeficiency Virus Type Progressive Multifocal Leukoencephalopathy Acquire Immune Deficiency Syndrome Progressive Multifocalleukoencephalopathy 
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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Kamel Khalili
    • 1
  • J. Paul Taylor
    • 1
  • Crystina Cupp
    • 1
  • Michael Zeira
    • 1
  • Shohreh Amini
    • 1
  1. 1.Molecular Neurovirology Section Jefferson Institute of Molecular MedicineThomas Jefferson UniversityPhiladelphiaUSA

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