Neurochemical Research

, Volume 29, Issue 5, pp 965–978

Multiple Actions of the Human Immunodeficiency Virus Type-1 Tat Protein on Microglial Cell Functions

  • Luisa Minghetti
  • Sergio Visentin
  • Mario Patrizio
  • Laura Franchini
  • Maria Antonietta Ajmone-Cat
  • Giulio Levi
Article

DOI: 10.1023/B:NERE.0000021241.90133.89

Cite this article as:
Minghetti, L., Visentin, S., Patrizio, M. et al. Neurochem Res (2004) 29: 965. doi:10.1023/B:NERE.0000021241.90133.89

Abstract

The human immunodeficiency virus type-1 (HIV-1) regulatory protein Tat is produced in the early phase of infection and is essential for virus replication. Together with other viral products, Tat has been implicated in the pathogenesis of HIV-1–associated dementia (HAD). As HIV-1 infection in the brain is very limited and macrophage/microglial cells are the only cellular type productively infected by the virus, it has been proposed that many of the viral neurotoxic effects are mediated by microglial products. We and others have shown that Tat affects the functional state of microglial cells, supporting the hypothesis that activated microglia play a role in the neuropathology associated with HIV-1 infection. This review describes the experimental evidence indicating that Tat stimulates microglia to synthesize potentially neurotoxic molecules, including proinflammatory cytokines and free radicals, and interferes with molecular mechanisms controlling cAMP levels, intracellular [Ca2+], and ion channel expression.

Brain macrophages cyclic AMP free radicals interleukin-1β isoprostane K+ channels nitric oxide tumor necrosis factor-α 

Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  • Luisa Minghetti
    • 1
  • Sergio Visentin
    • 1
  • Mario Patrizio
    • 1
  • Laura Franchini
    • 1
  • Maria Antonietta Ajmone-Cat
    • 1
  • Giulio Levi
    • 1
  1. 1.Department of Cell Biology and NeuroscienceIstituto Superiore di SanitàRomeItaly

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