HIV-1 Nef increases astrocyte sensitivity towards exogenous hydrogen peroxide.
BACKGROUND
HIV-1 infected individuals are under chronic exposure to reactive oxygen species (ROS) considered to be instrumental in the progression of AIDS and the development of HIV-1 associated dementia (HAD). Astrocytes support neuronal function and protect them against cytotoxic substances including ROS. The protein HIV-1 Nef, a progression factor in AIDS pathology is abundantly expressed in astrocytes in patients with HAD, and thus may influence its functions.


RESULTS
Endogenous expressed HIV-1 Nef leads to increased sensitivity of human astrocytes towards exogenous hydrogen peroxide but not towards TNF-alpha. Cell death of nef-expressing astrocytes exposed to 10 μM hydrogen peroxide for 30 min occurred within 4 h.


CONCLUSIONS
HIV-1 Nef may contribute to neuronal dysfunction and the development of HAD by causing death of astrocytes through decreasing their tolerance for hydrogen peroxide.
Institute of Virology, Technical University of Munich/Helmholtz Zentrum München, 81675 Munich, Germany.
Sabine
S
Masanetz
Michael H
MH
Lehmann
D001253:Astrocytes / Q000187:drug effects* / Q000821:virology*; D002460:Cell Line; D002470:Cell Survival; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D037521:Virulence Factors / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D037521:Virulence Factors; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D006861:Hydrogen Peroxide
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