title: Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response.
abstract: A dangerous cytokine storm occurs in the SARS involving in immune disorder, but many aspects of the pathogenetic mechanism remain obscure since its outbreak. To deeply reveal the interaction of host and SARS-CoV, based on the basic structural feature of pathogen-associated molecular pattern, we created a new bioinformatics method for searching potential pathogenic molecules and identified a set of SARS-CoV specific GU-rich ssRNA fragments with a high-density distribution in the genome. In vitro experiments, the result showed the representative SARS-CoV ssRNAs had powerful immunostimulatory activities to induce considerable level of pro-inflammatory cytokine TNF-a, IL-6 and IL-12 release via the TLR7 and TLR8, almost 2-fold higher than the strong stimulatory ssRNA40 that was found previously from other virus. Moreover, SARS-CoV ssRNA was able to cause acute lung injury in mice with a high mortality rate in vivo experiment. It suggests that SARS-CoV specific GU-rich ssRNA plays a very important role in the cytokine storm associated with a dysregulation of the innate immunity. This study not only presents new evidence about the immunopathologic damage caused by overactive inflammation during the SARS-CoV infection, but also provides a useful clue for a new therapeutic strategy.
authors.affiliation: Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. liyan.com@gmail.com
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Hongwei
authors.initials: H
authors.lastname: Cao
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jiang
authors.initials: J
authors.lastname: Zheng
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization / Q000379:methods; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D059372:Nucleotide Motifs; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000008:administration & dosage / Q000276:immunology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000473:pathology / Q000821:virology; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000276:immunology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015850:Interleukin-6; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D012367:RNA, Viral; C552579:TLR8 protein, mouse; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse