Replication rate of feline immunodeficiency virus in astrocytes is envelope dependent: Implications for glutamate uptake

Feline immunodeficiency virus (FIV) induces neurological abnormalities in d omestic cats. Previously, we demonstrated that two disparate strains of FIV (FIV-34TF10 and FIV-PPR) varied greatly in the ability to replicate in fel ine cortical astrocytes. To investigate the impact of the env region on the replication efficiency of these strains, we constructed two env chimera vi ruses, FIV-34TF10-PPRenv and FIV-PPR-34TF10env, to infect feline cortical a strocytes in vitro. Although all of these viruses infected cortical astrocy tes, the efficiency of replication depended on strain, and the env region p layed an essential role. The viruses containing the env of 34TF10, FIV-34TF 10, and FIV-PPR-34TF10env had the greatest replication rate, whereas the vi ruses containing the env of PPR replicated at a lower level. Other viral re gions had modulatory effects on the replication rate, with the FIV-PPR geno me providing a slight replication advantage over the FIV-34TF10 genome. We also monitored the effects of these viruses on an important astrocyte funct ion, glutamate uptake; all viruses significantly decreased this activity, b ut only the viruses containing the env of PPR significantly impaired glutam ate uptake without altering the culture viability. These results may be par ticularly relevant in the context of lentivirus-induced central nervous sys tem disease in which a selective breakdown of astroglial function may contr ibute to neurodegeneration. (C) 2000 Academic Press.