{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699995340947200.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.212519699"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.212519699"}}],"dc:title":[{"@value":"Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n            The 1918 influenza pandemic caused more than 20 million deaths worldwide. Thus, the potential impact of a re-emergent 1918 or 1918-like influenza virus, whether through natural means or as a result of bioterrorism, is of significant concern. The genetic determinants of the virulence of the 1918 virus have not been defined yet, nor have specific clinical prophylaxis and/or treatment interventions that would be effective against a re-emergent 1918 or 1918-like virus been identified. Based on the reported nucleotide sequences, we have reconstructed the hemagglutinin (HA), neuraminidase (NA), and matrix (M) genes of the 1918 virus. Under biosafety level 3 (agricultural) conditions, we have generated recombinant influenza viruses bearing the 1918 HA, NA, or M segments. Strikingly, recombinant viruses possessing both the 1918 HA and 1918 NA were virulent in mice. In contrast, a control virus with the HA and NA from a more recent human isolate was unable to kill mice at any dose tested. The recombinant viruses were also tested for their sensitivity to U.S. Food and Drug Administration-approved antiinfluenza virus drugs\n            <jats:italic>in vitro</jats:italic>\n            and\n            <jats:italic>in vivo</jats:italic>\n            . Recombinant viruses possessing the 1918 NA or both the 1918 HA and 1918 NA were inhibited effectively in both tissue culture and mice by the NA inhibitors, zanamivir and oseltamivir. A recombinant virus possessing the 1918 M segment was inhibited effectively both in tissue culture and\n            <jats:italic>in vivo</jats:italic>\n            by the M2 ion-channel inhibitors amantadine and rimantadine. These data suggest that current antiviral strategies would be effective in curbing the dangers of a re-emergent 1918 or 1918-like virus.\n          </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380857596201707014","@type":"Researcher","foaf:name":[{"@value":"Terrence M. Tumpey"}],"jpcoar:affiliationName":[{"@value":"Southeast Poultry Research Laboratory, United States Department of Agriculture, Athens, GA 30605; Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Rockville, MD 20850"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857596201707009","@type":"Researcher","foaf:name":[{"@value":"Adolfo García-Sastre"}],"jpcoar:affiliationName":[{"@value":"Southeast Poultry Research Laboratory, United States Department of Agriculture, Athens, GA 30605; Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Rockville, MD 20850"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857596201707013","@type":"Researcher","foaf:name":[{"@value":"Andrea Mikulasova"}],"jpcoar:affiliationName":[{"@value":"Southeast Poultry Research Laboratory, United States Department of Agriculture, Athens, GA 30605; Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Rockville, MD 20850"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857596201707011","@type":"Researcher","foaf:name":[{"@value":"Jeffery K. Taubenberger"}],"jpcoar:affiliationName":[{"@value":"Southeast Poultry Research Laboratory, United States Department of Agriculture, Athens, GA 30605; Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Rockville, MD 20850"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857596201707008","@type":"Researcher","foaf:name":[{"@value":"David E. Swayne"}],"jpcoar:affiliationName":[{"@value":"Southeast Poultry Research Laboratory, United States Department of Agriculture, Athens, GA 30605; Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Rockville, MD 20850"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857596201707010","@type":"Researcher","foaf:name":[{"@value":"Peter Palese"}],"jpcoar:affiliationName":[{"@value":"Southeast Poultry Research Laboratory, United States Department of Agriculture, Athens, GA 30605; Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Rockville, MD 20850"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857596201707012","@type":"Researcher","foaf:name":[{"@value":"Christopher F. Basler"}],"jpcoar:affiliationName":[{"@value":"Southeast Poultry Research Laboratory, United States Department of Agriculture, Athens, GA 30605; Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Rockville, MD 20850"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2002-10-04","prism:volume":"99","prism:number":"21","prism:startingPage":"13849","prism:endingPage":"13854"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.212519699"}],"createdAt":"2002-10-15","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050307900768925184","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"The host tropism of current zoonotic H7N9 viruses depends mainly on an acid-labile hemagglutinin with a single amino acid mutation in the stalk region"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285708465083776","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567182009522432","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Circulating Avian Influenza Viruses Closely Related to the 1918 Virus Have Pandemic Potential"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848658911857920","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH"}]},{"@id":"https://cir.nii.ac.jp/crid/1361412895887200000","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Oseltamivir Is Effective against 1918 Influenza Virus Infection of Macaques but Vulnerable to Escape"}]},{"@id":"https://cir.nii.ac.jp/crid/1363664919037955200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Infection of Human Tracheal Epithelial Cells by H5 Avian Influenza Virus Is Regulated by the Acid Stability of Hemagglutinin and the pH of Target Cell Endosomes"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204172371712","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"A Fourth Scale Sensitive to the Magnetic Field; Intermolecular Frequency Symmetry in a Specific Interaction between Protein and Low-Molecular Compound"},{"@value":"Communication to the editor: A fourth scale sensitive to the magnetic field: intermolecular frequency symmetry in a specific interaction between protein and low-molecular compound"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.212519699"},{"@type":"CROSSREF","@value":"10.1038/s41598-018-31397-3_references_DOI_8JXgCiLBBSSsrJDez3nV3HnDmtN"},{"@type":"CROSSREF","@value":"10.1371/journal.ppat.1012427_references_DOI_8JXgCiLBBSSsrJDez3nV3HnDmtN"},{"@type":"CROSSREF","@value":"10.1074/jbc.m114.611327_references_DOI_8JXgCiLBBSSsrJDez3nV3HnDmtN"},{"@type":"CROSSREF","@value":"10.1248/cpb.58.1669_references_DOI_8JXgCiLBBSSsrJDez3nV3HnDmtN"},{"@type":"CROSSREF","@value":"10.1016/j.chom.2014.05.006_references_DOI_8JXgCiLBBSSsrJDez3nV3HnDmtN"},{"@type":"CROSSREF","@value":"10.1128/mbio.02059-19_references_DOI_8JXgCiLBBSSsrJDez3nV3HnDmtN"},{"@type":"CROSSREF","@value":"10.3390/v12010082_references_DOI_8JXgCiLBBSSsrJDez3nV3HnDmtN"}]}