Catecholamine-mediated inactivation of poliovirus RNA.
Catecholamine (DOPA, dopamine, epinephrine, or norepinephrine) and Cu2+ produced a potent inactivator(s) of transfectivity of poliovirus RNA. Al3+, Co2+, Fe3+, Mn2+, Ni2+, Sn4+ and Zn2+ did not substitute for Cu2+. Potency of inactivator(s) was eliminated by chelator (EDTA, histamine, or L-histidine). Kinetics of inactivation was single-hit, and inactivation was first order with respect to inactivator(s). A method for estimating relative concentration of inactivator(s) showed its course of production at 23 degrees C from norepinephrine at 10 microM and Cu2+ at 1.0 microM: under air, inactivator(s) peaked after 95 min, then decayed; under oxygen, peak was after 40 min; and under nitrogen, no production was detected. After prolonged exposure, most of the tritium from tritiated viral RNA appeared in small fragments. As tested with Cu2+ and norepinephrine, Al3+ and Fe3+ interfered strongly with production of inactivator(s) but not with preformed inactivator(s). An inactivator role for copper complexes of the semiquinone derivatives is hypothesized.
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Department of Pathology and Microbiology, University of Nebraska, College of Medicine, Omaha 68105.
D000998:Antiviral Agents / Q000096:biosynthesis / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D007700:Kinetics; D008670:Metals / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D017955:Poliovirus / Q000187:drug effects*; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000187:drug effects*
D000998:Antiviral Agents; D002395:Catecholamines; D002614:Chelating Agents; D008670:Metals; D012367:RNA, Viral; D003300:Copper; D009638:Norepinephrine