Effects of feline immunodeficiency virus on astrocyte glutamate uptake: implications for lentivirus-induced central nervous system diseases.
Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that causes a spectrum of diseases remarkably similar to AIDS in HIV-infected humans. As part of this spectrum, both HIV-1 and FIV induce neurologic disorders. Because astrocytes are essential in maintaining the homeostasis of the central nervous system, we analyzed FIV for the ability to infect feline astrocytes. Through immunocytochemistry and reverse transcriptase activity, it was demonstrated that two molecular clones of FIV (FIV-34TF10 and FIV-PPR) produce a chronic low level productive infection of feline astrocyte cultures. To investigate the consequences of this infection, selected astrocyte functions were examined. Infection with FIV-34TF10 significantly decreased the ability of astrocytes to scavenge extracellular glutamate (with a peak inhibition of 74%). The effects of the infection did not appear to be a result of toxicity but rather were more selective in nature because the glucose uptake function of the infected astrocyte cultures was not altered. Our data demonstrate that FIV productively infected, at a low level, feline astrocyte cultures, and as a consequence of this infection, an important astroglial function was altered. These findings suggest that a chronic low grade infection of astrocytes may impair the ability of these cells to maintain homeostasis of the central nervous system that, in turn, may contribute to a neurodegenerative disease process that is often associated with lentivirus infections.
Yu
N
N
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Billaud
J N
JN
Phillips
T R
TR
D000818:Animals; D001253:Astrocytes / Q000502:physiology* / Q000821:virology*; D001692:Biological Transport; D002415:Cats; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000821:virology*; D002540:Cerebral Cortex / Q000502:physiology / Q000821:virology; D003847:Deoxyglucose / Q000378:metabolism*; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D005971:Glutamates / Q000378:metabolism*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000502:physiology*; D007700:Kinetics; D016180:Lentivirus Infections / Q000503:physiopathology / Q000821:virology; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication
D005904:Glial Fibrillary Acidic Protein; D005971:Glutamates; D014764:Viral Proteins; D003847:Deoxyglucose