Chloride concentration discriminates between Foot-and-mouth disease virus ires-dependent translation and classical scanning translation: new aspects of the picornavirus shutoff mechanism.
Some picornaviruses might use the general increase of ionic strength in the host cell that occurs successively after infection to induce shutoff of host protein synthesis and to stimulate viral protein synthesis. In order to investigate this discrimination mode on a molecular level, in vitro experiments under different salt conditions comparing the Foot-and-mouth disease virus (FMDV) internal ribosome entry site (IRES)-dependent translation with the translation via the classical scanning mechanism were performed. For classical mRNA optimum concentrations of all investigated salts ranged between 70 and 100 mmol/l. However, for FMDV IRES-dependent translation the optima depended strongly on the anion used. While acetates caused only a weak stimulation of translation efficiency with maxima ranging between 150 and 180 mmol/l, chlorides lead to a strong stimulation with maxima ranging between 120 and 150 mmol/l. Competition experiments revealed that the concentration of chlorides had a greater influence on the discrimination between cellular and viral RNA translation than the total ionic strength. Taken together, the data support a model in which a specific increase in the chloride concentration rather than a general increase in the ionic strength is responsible for the shutoff effect induced by some picornaviruses.
Schmidt-Brauns
J
J
Max-Planck-Institute for Marine Microbiology, Celsiusstr. 1, 28359 Bremen, Germany. jschmidt@mpi-bremen.de
D002414:Cations, Monovalent / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology*; D029544:Foot-and-Mouth Disease Virus / Q000187:drug effects / Q000235:genetics*; D066298:In Vitro Techniques; D010849:Picornaviridae / Q000187:drug effects* / Q000235:genetics; D011189:Potassium Chloride / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000187:drug effects*; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D012964:Sodium / Q000494:pharmacology
D002414:Cations, Monovalent; D002712:Chlorides; D012367:RNA, Viral; D011189:Potassium Chloride; D012964:Sodium