title: Class I ADP-ribosylation factors are involved in enterovirus 71 replication.
abstract: Enterovirus 71 is one of the major causative agents of hand, foot, and mouth disease in infants and children. Replication of enterovirus 71 depends on host cellular factors. The viral replication complex is formed in novel, cytoplasmic, vesicular compartments. It has not been elucidated which cellular pathways are hijacked by the virus to create these vesicles. Here, we investigated whether proteins associated with the cellular secretory pathway were involved in enterovirus 71 replication. We used a loss-of-function assay, based on small interfering RNA. We showed that enterovirus 71 RNA replication was dependent on the activity of Class I ADP-ribosylation factors. Simultaneous depletion of ADP-ribosylation factors 1 and 3, but not three others, inhibited viral replication in cells. We also demonstrated with various techniques that the brefeldin-A-sensitive guanidine nucleotide exchange factor, GBF1, was critically important for enterovirus 71 replication. Our results suggested that enterovirus 71 replication depended on GBF1-mediated activation of Class I ADP-ribosylation factors. These results revealed a connection between enterovirus 71 replication and the cellular secretory pathway; this pathway may represent a novel target for antiviral therapies.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Du
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics* / Q000378:metabolism; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D020126:Brefeldin A / Q000494:pharmacology; D002460:Cell Line; D029821:Enterovirus A, Human / Q000187:drug effects / Q000502:physiology*; D004769:Enterovirus Infections / Q000235:genetics* / Q000821:virology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D011485:Protein Binding; D015854:Up-Regulation; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: C120445:GBF1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D014764:Viral Proteins; D020126:Brefeldin A; C116687:ARF3 protein, human; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors