Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets
Here we report the isolation of the influenza A/H1N1 2009 pandemic (A/H1N1pdm) and A/H3N2 viruses carrying an I38T mutation in the polymerase acidic protein—a mutation that confers reduced susceptibility to baloxavir marboxil—from patients before and after treatment with baloxavir marboxil in Japan....
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| Veröffentlicht in: | Nature microbiology 2020-01, Vol.5 (1), p.27-33 |
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| creator | Imai, Masaki Yamashita, Makoto Sakai-Tagawa, Yuko Iwatsuki-Horimoto, Kiyoko Kiso, Maki Murakami, Jurika Yasuhara, Atsuhiro Takada, Kosuke Ito, Mutsumi Nakajima, Noriko Takahashi, Kenta Lopes, Tiago J. S. Dutta, Jayeeta Khan, Zenab Kriti, Divya van Bakel, Harm Tokita, Akifumi Hagiwara, Haruhisa Izumida, Naomi Kuroki, Haruo Nishino, Tamon Wada, Noriyuki Koga, Michiko Adachi, Eisuke Jubishi, Daisuke Hasegawa, Hideki Kawaoka, Yoshihiro |
| description | Here we report the isolation of the influenza A/H1N1 2009 pandemic (A/H1N1pdm) and A/H3N2 viruses carrying an I38T mutation in the polymerase acidic protein—a mutation that confers reduced susceptibility to baloxavir marboxil—from patients before and after treatment with baloxavir marboxil in Japan. These variants showed replicative abilities and pathogenicity that is similar to those of wild-type isolates in hamsters; they also transmitted efficiently between ferrets by respiratory droplets.
Resistance to baloxavir marboxil, a recently approved drug to treat influenza infection, was thought to make the virus less fit. This study reports that resistant viruses isolated from Japanese patients have normal replicative abilities and pathogenicity in animal models and thus might spread in humans. |
| doi_str_mv | 10.1038/s41564-019-0609-0 |
| format | Article |
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Resistance to baloxavir marboxil, a recently approved drug to treat influenza infection, was thought to make the virus less fit. This study reports that resistant viruses isolated from Japanese patients have normal replicative abilities and pathogenicity in animal models and thus might spread in humans.</description><identifier>ISSN: 2058-5276</identifier><identifier>EISSN: 2058-5276</identifier><identifier>DOI: 10.1038/s41564-019-0609-0</identifier><identifier>PMID: 31768027</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/23 ; 631/326 ; 631/326/22 ; 631/326/596/1578 ; 692/420 ; Animals ; Antiviral Agents - pharmacology ; Biomedical and Life Sciences ; Brief Communication ; Cricetinae ; Dibenzothiepins ; Drug Resistance, Viral ; Ferrets ; Humans ; Infectious Diseases ; Influenza ; Influenza A ; Influenza A virus - drug effects ; Influenza A virus - isolation & purification ; Influenza A virus - pathogenicity ; Influenza A virus - physiology ; Influenza, Human - transmission ; Influenza, Human - virology ; Japan ; Life Sciences ; Medical Microbiology ; Mice ; Microbiology ; Morpholines ; Mutation ; Nasal Lavage Fluid - virology ; Orthomyxoviridae Infections - transmission ; Orthomyxoviridae Infections - virology ; Oxazines - pharmacology ; Pandemics ; Parasitology ; Pathogenicity ; Pyridines - pharmacology ; Pyridones ; RNA-Dependent RNA Polymerase - genetics ; Thiepins - pharmacology ; Triazines - pharmacology ; Viral Proteins - genetics ; Virology ; Virulence ; Virus Replication</subject><ispartof>Nature microbiology, 2020-01, Vol.5 (1), p.27-33</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019</rights><rights>Copyright Nature Publishing Group Jan 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-c2bf93cfc3d041b7bf47c383b19387ff3ee4dc69e2986da24e96687ccb17de403</citedby><cites>FETCH-LOGICAL-c372t-c2bf93cfc3d041b7bf47c383b19387ff3ee4dc69e2986da24e96687ccb17de403</cites><orcidid>0000-0002-9357-5588 ; 0000-0002-1376-6916 ; 0000-0001-5061-8296 ; 0000-0001-6988-1975 ; 0000-0002-8266-020X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41564-019-0609-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41564-019-0609-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31768027$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Imai, Masaki</creatorcontrib><creatorcontrib>Yamashita, Makoto</creatorcontrib><creatorcontrib>Sakai-Tagawa, Yuko</creatorcontrib><creatorcontrib>Iwatsuki-Horimoto, Kiyoko</creatorcontrib><creatorcontrib>Kiso, Maki</creatorcontrib><creatorcontrib>Murakami, Jurika</creatorcontrib><creatorcontrib>Yasuhara, Atsuhiro</creatorcontrib><creatorcontrib>Takada, Kosuke</creatorcontrib><creatorcontrib>Ito, Mutsumi</creatorcontrib><creatorcontrib>Nakajima, Noriko</creatorcontrib><creatorcontrib>Takahashi, Kenta</creatorcontrib><creatorcontrib>Lopes, Tiago J. S.</creatorcontrib><creatorcontrib>Dutta, Jayeeta</creatorcontrib><creatorcontrib>Khan, Zenab</creatorcontrib><creatorcontrib>Kriti, Divya</creatorcontrib><creatorcontrib>van Bakel, Harm</creatorcontrib><creatorcontrib>Tokita, Akifumi</creatorcontrib><creatorcontrib>Hagiwara, Haruhisa</creatorcontrib><creatorcontrib>Izumida, Naomi</creatorcontrib><creatorcontrib>Kuroki, Haruo</creatorcontrib><creatorcontrib>Nishino, Tamon</creatorcontrib><creatorcontrib>Wada, Noriyuki</creatorcontrib><creatorcontrib>Koga, Michiko</creatorcontrib><creatorcontrib>Adachi, Eisuke</creatorcontrib><creatorcontrib>Jubishi, Daisuke</creatorcontrib><creatorcontrib>Hasegawa, Hideki</creatorcontrib><creatorcontrib>Kawaoka, Yoshihiro</creatorcontrib><title>Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets</title><title>Nature microbiology</title><addtitle>Nat Microbiol</addtitle><addtitle>Nat Microbiol</addtitle><description>Here we report the isolation of the influenza A/H1N1 2009 pandemic (A/H1N1pdm) and A/H3N2 viruses carrying an I38T mutation in the polymerase acidic protein—a mutation that confers reduced susceptibility to baloxavir marboxil—from patients before and after treatment with baloxavir marboxil in Japan. These variants showed replicative abilities and pathogenicity that is similar to those of wild-type isolates in hamsters; they also transmitted efficiently between ferrets by respiratory droplets.
Resistance to baloxavir marboxil, a recently approved drug to treat influenza infection, was thought to make the virus less fit. 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S. ; Dutta, Jayeeta ; Khan, Zenab ; Kriti, Divya ; van Bakel, Harm ; Tokita, Akifumi ; Hagiwara, Haruhisa ; Izumida, Naomi ; Kuroki, Haruo ; Nishino, Tamon ; Wada, Noriyuki ; Koga, Michiko ; Adachi, Eisuke ; Jubishi, Daisuke ; Hasegawa, Hideki ; Kawaoka, Yoshihiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-c2bf93cfc3d041b7bf47c383b19387ff3ee4dc69e2986da24e96687ccb17de403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>45/23</topic><topic>631/326</topic><topic>631/326/22</topic><topic>631/326/596/1578</topic><topic>692/420</topic><topic>Animals</topic><topic>Antiviral Agents - pharmacology</topic><topic>Biomedical and Life Sciences</topic><topic>Brief Communication</topic><topic>Cricetinae</topic><topic>Dibenzothiepins</topic><topic>Drug Resistance, Viral</topic><topic>Ferrets</topic><topic>Humans</topic><topic>Infectious Diseases</topic><topic>Influenza</topic><topic>Influenza A</topic><topic>Influenza A virus - drug effects</topic><topic>Influenza A virus - isolation & purification</topic><topic>Influenza A virus - pathogenicity</topic><topic>Influenza A virus - physiology</topic><topic>Influenza, Human - transmission</topic><topic>Influenza, Human - virology</topic><topic>Japan</topic><topic>Life Sciences</topic><topic>Medical Microbiology</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Morpholines</topic><topic>Mutation</topic><topic>Nasal Lavage Fluid - virology</topic><topic>Orthomyxoviridae Infections - transmission</topic><topic>Orthomyxoviridae Infections - virology</topic><topic>Oxazines - pharmacology</topic><topic>Pandemics</topic><topic>Parasitology</topic><topic>Pathogenicity</topic><topic>Pyridines - pharmacology</topic><topic>Pyridones</topic><topic>RNA-Dependent RNA Polymerase - genetics</topic><topic>Thiepins - pharmacology</topic><topic>Triazines - pharmacology</topic><topic>Viral Proteins - genetics</topic><topic>Virology</topic><topic>Virulence</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Imai, Masaki</creatorcontrib><creatorcontrib>Yamashita, Makoto</creatorcontrib><creatorcontrib>Sakai-Tagawa, Yuko</creatorcontrib><creatorcontrib>Iwatsuki-Horimoto, Kiyoko</creatorcontrib><creatorcontrib>Kiso, Maki</creatorcontrib><creatorcontrib>Murakami, Jurika</creatorcontrib><creatorcontrib>Yasuhara, Atsuhiro</creatorcontrib><creatorcontrib>Takada, Kosuke</creatorcontrib><creatorcontrib>Ito, Mutsumi</creatorcontrib><creatorcontrib>Nakajima, Noriko</creatorcontrib><creatorcontrib>Takahashi, Kenta</creatorcontrib><creatorcontrib>Lopes, Tiago J. 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These variants showed replicative abilities and pathogenicity that is similar to those of wild-type isolates in hamsters; they also transmitted efficiently between ferrets by respiratory droplets.
Resistance to baloxavir marboxil, a recently approved drug to treat influenza infection, was thought to make the virus less fit. This study reports that resistant viruses isolated from Japanese patients have normal replicative abilities and pathogenicity in animal models and thus might spread in humans.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31768027</pmid><doi>10.1038/s41564-019-0609-0</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-9357-5588</orcidid><orcidid>https://orcid.org/0000-0002-1376-6916</orcidid><orcidid>https://orcid.org/0000-0001-5061-8296</orcidid><orcidid>https://orcid.org/0000-0001-6988-1975</orcidid><orcidid>https://orcid.org/0000-0002-8266-020X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2058-5276 |
| ispartof | Nature microbiology, 2020-01, Vol.5 (1), p.27-33 |
| issn | 2058-5276 2058-5276 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2318733039 |
| source | MEDLINE; SpringerLink Journals |
| subjects | 45/23 631/326 631/326/22 631/326/596/1578 692/420 Animals Antiviral Agents - pharmacology Biomedical and Life Sciences Brief Communication Cricetinae Dibenzothiepins Drug Resistance, Viral Ferrets Humans Infectious Diseases Influenza Influenza A Influenza A virus - drug effects Influenza A virus - isolation & purification Influenza A virus - pathogenicity Influenza A virus - physiology Influenza, Human - transmission Influenza, Human - virology Japan Life Sciences Medical Microbiology Mice Microbiology Morpholines Mutation Nasal Lavage Fluid - virology Orthomyxoviridae Infections - transmission Orthomyxoviridae Infections - virology Oxazines - pharmacology Pandemics Parasitology Pathogenicity Pyridines - pharmacology Pyridones RNA-Dependent RNA Polymerase - genetics Thiepins - pharmacology Triazines - pharmacology Viral Proteins - genetics Virology Virulence Virus Replication |
| title | Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets |
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