0000000000637110
AUTHOR
M. Kelve
Modulation of the Antiviral 2-5A System in Human Immunodeficiency Virus-1-Infected CEM Cells by Propentofylline
2′,5′-OIigoadenylates (2-5A) play an essential role in the establishment of the antiviral state of cells exposed to virus infection. However, - after an initial increase observed in some cell lines - the activity of the interferon (IFN)-inducible, 2-5A-forming 2′,5′-oligoadenylate synthetase (2-5A synthetase) strongly decreases soon after infection of cells with the human immunodeficiency virus-1 (HIV-1). In the present report, we show that in IFN-treated human T lymphoblastoid CEM cells, the decrease in 2-5A synthetase activity had already occurred at day 1 post infection (p.i.)- At days 3 and 5 p.i., the 2-5A synthetase activity in the IFN-treated infected cells amounted to only 10-12% of…
Homologies Between Different Forms of 2-5A Synthetases
(2′-5′) Oligoadenylate synthetases (2-5A synthetases; EC 2.7.7.19) are present in mammalian cells and tissues and synthesize from ATP a series of oligomers termed 2-5A [general formula: ppp(A2′p)nA; with 1 ≤ n < 18 and usually 1 ≤ n < 6] (Hovanessian 1991). For full enzymic activity of the 2-5A synthetases, binding of double-stranded RNA is required (Sen 1982). Three principal 2-5A synthetase isoenzymes have been described with Mr’s of 40–46, 69, and 100 kDa (Chebath et al. 1987; Hovanessian et al. 1987, 1988). In the following they are classified as 2-5A synthetase I [Mr 40–46 000], II [Mr 69 000] and III [Mr 100 000]. All three isoforms are induced in cells by interferon (Cohen et al. 198…
The 2-5A System and HIV Infection
The human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired immunodeficiency syndrome (AIDS). The progression of this retro viral disease is associated with various clinical manifestations, including the acquisition of an immunodeficient state, the frequent presence of neurological disorders, and some malignancies (reviewed in Barre-Sinoussi et al. 1983; Wong-Staal and Gallo 1985; Fauci 1988). Immunologic dysfunctions caused by HIV-1 infection include disorders in the production of cytokines (Murray et al. 1984; Abb et al. 1986). For example, a significant decrease in the production of interferon-α (IFN-α) by cultured peripheral blood mononuclear cells (PBMC) from pat…
Neurotoxicity in Rat Cortical Cells Caused by N-Methyl-D-Aspartate (NMDA) and gp120 of HIV-1: Induction and Pharmacological Intervention
Incubation of highly enriched neurons from rat cerebral cortex with the human immunodeficiency virus type 1 (HIV-1) coat protein gpl20 for 18 h results in fragmentation of DNA at internucleosomal linkers, a feature of apoptosis. We report that neurons respond to exposure to gp120 with an increased release of arachidonic acid via activation of phospholipase A2. This process is not inhibited by antagonists of the N-methyl-D-aspartate (NMDA) receptor channels. To investigate the influence of arachidonic acid on the sensitivity of NMDA receptor towards its aganist, low concentrations of NMDA were coadministered with arachidonic acid. Under these conditions the NMDA-mediated cytotoxicity was enh…