title: Difference in susceptibility to MxA protein between a coxsackievirus B1 isolate and prototype, impact of serial cell culture passage.
abstract: Human enteroviruses (EVs) cause a broad spectrum of acute and chronic diseases including meningitis and myocarditis. The type I interferon-induced MxA protein has been shown to inhibit the replication of an EV, coxsackievirus B4 (CVB4), but not cardioviruses such as encephalomyocarditis virus and mengo virus, members of the Picornaviridae family. EVs consist of more than 60 distinct serotypes against which the antiviral activity of MxA was not investigated yet. The main aim of this study was to explore the antiviral activity of MxA protein against a clinical CVB1 isolate and other EV prototypes. Vero cells expressing constituvely MxA protein were infected with EVs, and the percentage of inhibiton of expression of enteroviral RNA and capsid VP1 protein was determined. Following infection of MxA-transfected Vero cells with EVs, the expression of enteroviral RNA was inhibited by up to 99%, and that of VP1 protein by up to 85%. However, there was a difference in the percentage of MxA inhibition of EV replication between the different EV prototypes. This difference in MxA sensitivity was not due to a difference in the viral replication rates. The MxA protein was inactive against the clinical CVB1 isolate, and the replication rate of CVB1 isolate in MxA-transfected Vero cells was higher than that in mock-transfected Vero cells. A serial passage of the clinical CVB1 isolate and other EV prototypes resulted in an increase in their susceptibility to MxA protein. These results suggest the presence of MxA-resistant EV variants that may escape innate immunity and cause disease. J. Med. Virol. 82:424-432, 2010. (c) 2010 Wiley-Liss, Inc.
authors.affiliation: Faculty of Medicine, Virology Unit, Department of Microbiology, Kuwait University, Safat, Kuwait. wchehadeh@hsc.edu.kw
authors.forename: Wassim
authors.initials: W
authors.lastname: Chehadeh
authors.forename: Hayfaa A
authors.initials: HA
authors.lastname: Abdulkareem
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D002648:Child; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000821:virology; D029822:Enterovirus B, Human / Q000276:immunology* / Q000302:isolation & purification*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D064547:Myxovirus Resistance Proteins; D012692:Serial Passage; D014709:Vero Cells; D014779:Virus Replication
chemical_list: C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D019204:GTP-Binding Proteins