title: Differential Regulation of TLR Signaling on the Induction of Antiviral Interferons in Human Intestinal Epithelial Cells Infected with Enterovirus 71.
abstract: Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-α, -β, -ω, -κ, and -ε decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection.
authors.affiliation: Medical School, Jiangsu Provincial Key Laboratory of Medicine, and the State Key Laboratory of Pharmaceutical Technology, Nanjing University, Nanjing, China.|Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Medical School, Jiangsu Provincial Key Laboratory of Medicine, and the State Key Laboratory of Pharmaceutical Technology, Nanjing University, Nanjing, China.|Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Lianfu
authors.initials: L
authors.lastname: Ji
authors.affiliation: Medical School, Jiangsu Provincial Key Laboratory of Medicine, and the State Key Laboratory of Pharmaceutical Technology, Nanjing University, Nanjing, China.|Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Medical School, Jiangsu Provincial Key Laboratory of Medicine, and the State Key Laboratory of Pharmaceutical Technology, Nanjing University, Nanjing, China.|Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Minnesota at Twin Cities, Saint Paul, Minnesota, United States of America.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Cardona
authors.affiliation: Medical School, Jiangsu Provincial Key Laboratory of Medicine, and the State Key Laboratory of Pharmaceutical Technology, Nanjing University, Nanjing, China.|Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Minnesota at Twin Cities, Saint Paul, Minnesota, United States of America.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xing
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology; D015153:Blotting, Western; D029821:Enterovirus A, Human; D004769:Enterovirus Infections / Q000378:metabolism* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D019073:HT29 Cells / Q000378:metabolism / Q000502:physiology / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000378:metabolism / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000502:physiology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C470409:TICAM1 protein, human; D051193:Toll-Like Receptors; D007372:Interferons