title: Cellular mRNA decay protein AUF1 negatively regulates enterovirus and human rhinovirus infections.
abstract: To successfully complete their replication cycles, picornaviruses modify several host proteins to alter the cellular environment to favor virus production. One such target of viral proteinase cleavage is AU-rich binding factor 1 (AUF1), a cellular protein that binds to AU-rich elements, or AREs, in the 3' noncoding regions (NCRs) of mRNAs to affect the stability of the RNA. Previous studies found that, during poliovirus or human rhinovirus infection, AUF1 is cleaved by the viral proteinase 3CD and that AUF1 can interact with the long 5' NCR of these viruses in vitro. Here, we expand on these initial findings to demonstrate that all four isoforms of AUF1 bind directly to stem-loop IV of the poliovirus 5' NCR, an interaction that is inhibited through proteolytic cleavage of AUF1 by the viral proteinase 3CD. Endogenous AUF1 was observed to relocalize to the cytoplasm of infected cells in a viral protein 2A-driven manner and to partially colocalize with the viral protein 3CD. We identify a negative role for AUF1 in poliovirus infection, as AUF1 inhibited viral translation and, ultimately, overall viral titers. Our findings also demonstrate that AUF1 functions as an antiviral factor during infection by coxsackievirus or human rhinovirus, suggesting a common mechanism that targets these related picornaviruses.
authors.affiliation: Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697 USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cathcart
authors.forename: Janet M
authors.initials: JM
authors.lastname: Rozovics
authors.forename: Bert L
authors.initials: BL
authors.lastname: Semler
mesh_terms: D000086042:3C Viral Proteases; D000818:Animals; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D024202:Electrophoretic Mobility Shift Assay; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism / Q000821:virology; D004770:Enterovirus / Q000472:pathogenicity*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010850:Picornaviridae Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D017955:Poliovirus / Q000235:genetics; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D020871:RNA Stability; D022661:RNA, Untranslated / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D011817:Rabbits; D012229:Rhinovirus / Q000472:pathogenicity*; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D020033:Protein Isoforms; D022661:RNA, Untranslated; D012367:RNA, Viral; D014764:Viral Proteins; C074995:viral protein 1, rhinovirus; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases
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