A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets
Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants...
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| Published in | Cell host & microbe Vol. 22; no. 5; pp. 615 - 626.e8 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
08.11.2017
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored.
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•Highly pathogenic avian influenza (HPAI) H7N9 viruses replicate efficiently in mammals•HPAI H7N9 viruses are more pathogenic than low pathogenic H7N9 viruses in mammals•HPAI H7N9 viruses transmit via respiratory droplets among ferrets•HPAI H7N9 viruses show low sensitivity to neuraminidase inhibitors in mice
Highly pathogenic avian influenza (HPAI) H7N9 viruses have emerged and raised concerns of a pandemic. Imai et al. characterized an HPAI H7N9 virus isolated from a human. This virus transmitted among ferrets without prior adaptation and caused lethal infection in animals, demonstrating its pandemic potential and the need for surveillance. |
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| AbstractList | Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored.Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored. Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored. Low pathogenic H7N9 influenza has recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo , but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored. Highly pathogenic avian influenza (HPAI) H7N9 viruses have emerged and raised concerns of a pandemic. Imai et al. characterized an HPAI H7N9 virus isolated from a human. This virus transmitted among ferrets without prior adaptation and caused lethal infection in animals, demonstrating its pandemic potential and the need for surveillance. Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored. [Display omitted] •Highly pathogenic avian influenza (HPAI) H7N9 viruses replicate efficiently in mammals•HPAI H7N9 viruses are more pathogenic than low pathogenic H7N9 viruses in mammals•HPAI H7N9 viruses transmit via respiratory droplets among ferrets•HPAI H7N9 viruses show low sensitivity to neuraminidase inhibitors in mice Highly pathogenic avian influenza (HPAI) H7N9 viruses have emerged and raised concerns of a pandemic. Imai et al. characterized an HPAI H7N9 virus isolated from a human. This virus transmitted among ferrets without prior adaptation and caused lethal infection in animals, demonstrating its pandemic potential and the need for surveillance. |
| Author | Thompson, Andrew J. Nakao, Tomomi Takashita, Emi Shirakura, Masayuki Watanabe, Tokiko Yamayoshi, Seiya Nakajima, Noriko Yamashita, Makoto Odagiri, Takato Zhong, Gongxun Imai, Masaki Takahashi, Kenta Oishi, Kohei Watanabe, Shinji Mitake, Hiromichi Iwatsuki-Horimoto, Kiyoko Yasuhara, Atsuhiro Fujisaki, Seiichiro Kiso, Maki McBride, Ryan Takada, Kosuke Fukuyama, Satoshi Lopes, Tiago J.S. Kawaoka, Yoshihiro Hatta, Masato Sakai-Tagawa, Yuko Neumann, Gabriele Paulson, James C. Ito, Mutsumi Maemura, Tadashi Yamada, Shinya Fan, Shufang Hasegawa, Hideki Chiba, Shiho Shu, Yuelong |
| AuthorAffiliation | 1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan 7 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan 2 Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan 3 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA 6 National Institute for Viral Disease Control and Prevention, China Centers for Disease Control and Prevention, Beijing 102206, China 5 Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA 4 Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan |
| AuthorAffiliation_xml | – name: 3 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA – name: 6 National Institute for Viral Disease Control and Prevention, China Centers for Disease Control and Prevention, Beijing 102206, China – name: 4 Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan – name: 7 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – name: 2 Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan – name: 5 Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA – name: 1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan |
| Author_xml | – sequence: 1 givenname: Masaki surname: Imai fullname: Imai, Masaki email: mimai@ims.u-tokyo.ac.jp organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 2 givenname: Tokiko surname: Watanabe fullname: Watanabe, Tokiko organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 3 givenname: Maki surname: Kiso fullname: Kiso, Maki organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 4 givenname: Noriko surname: Nakajima fullname: Nakajima, Noriko organization: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan – sequence: 5 givenname: Seiya surname: Yamayoshi fullname: Yamayoshi, Seiya organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 6 givenname: Kiyoko surname: Iwatsuki-Horimoto fullname: Iwatsuki-Horimoto, Kiyoko organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 7 givenname: Masato surname: Hatta fullname: Hatta, Masato organization: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA – sequence: 8 givenname: Shinya surname: Yamada fullname: Yamada, Shinya organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 9 givenname: Mutsumi surname: Ito fullname: Ito, Mutsumi organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 10 givenname: Yuko surname: Sakai-Tagawa fullname: Sakai-Tagawa, Yuko organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 11 givenname: Masayuki surname: Shirakura fullname: Shirakura, Masayuki organization: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan – sequence: 12 givenname: Emi surname: Takashita fullname: Takashita, Emi organization: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan – sequence: 13 givenname: Seiichiro surname: Fujisaki fullname: Fujisaki, Seiichiro organization: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan – sequence: 14 givenname: Ryan surname: McBride fullname: McBride, Ryan organization: Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA – sequence: 15 givenname: Andrew J. surname: Thompson fullname: Thompson, Andrew J. organization: Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA – sequence: 16 givenname: Kenta surname: Takahashi fullname: Takahashi, Kenta organization: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan – sequence: 17 givenname: Tadashi surname: Maemura fullname: Maemura, Tadashi organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 18 givenname: Hiromichi surname: Mitake fullname: Mitake, Hiromichi organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 19 givenname: Shiho surname: Chiba fullname: Chiba, Shiho organization: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA – sequence: 20 givenname: Gongxun surname: Zhong fullname: Zhong, Gongxun organization: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA – sequence: 21 givenname: Shufang surname: Fan fullname: Fan, Shufang organization: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA – sequence: 22 givenname: Kohei surname: Oishi fullname: Oishi, Kohei organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 23 givenname: Atsuhiro surname: Yasuhara fullname: Yasuhara, Atsuhiro organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 24 givenname: Kosuke surname: Takada fullname: Takada, Kosuke organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 25 givenname: Tomomi surname: Nakao fullname: Nakao, Tomomi organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 26 givenname: Satoshi surname: Fukuyama fullname: Fukuyama, Satoshi organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 27 givenname: Makoto surname: Yamashita fullname: Yamashita, Makoto organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 28 givenname: Tiago J.S. surname: Lopes fullname: Lopes, Tiago J.S. organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan – sequence: 29 givenname: Gabriele surname: Neumann fullname: Neumann, Gabriele organization: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA – sequence: 30 givenname: Takato surname: Odagiri fullname: Odagiri, Takato organization: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan – sequence: 31 givenname: Shinji surname: Watanabe fullname: Watanabe, Shinji organization: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan – sequence: 32 givenname: Yuelong surname: Shu fullname: Shu, Yuelong organization: National Institute for Viral Disease Control and Prevention, China Centers for Disease Control and Prevention, Beijing 102206, China – sequence: 33 givenname: James C. surname: Paulson fullname: Paulson, James C. organization: Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA – sequence: 34 givenname: Hideki surname: Hasegawa fullname: Hasegawa, Hideki organization: Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan – sequence: 35 givenname: Yoshihiro surname: Kawaoka fullname: Kawaoka, Yoshihiro email: yoshihiro.kawaoka@wisc.edu organization: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29056430$$D View this record in MEDLINE/PubMed |
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| Keywords | antiviral sensitivity pathogenicity receptor-binding specificity ferrets transmissibility replication capacity nonhuman primates highly pathogenic avian influenza H7N9 viruses mice |
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| Snippet | Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire... Low pathogenic H7N9 influenza has recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient... |
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| SubjectTerms | Animals Antiviral Agents - pharmacology antiviral sensitivity Brain - pathology Brain - virology Cell Line Chickens - virology Conjunctiva - pathology Conjunctiva - virology Disease Models, Animal Enzyme Inhibitors - pharmacology ferrets Ferrets - virology highly pathogenic avian influenza H7N9 viruses Humans Influenza A Virus, H7N9 Subtype - isolation & purification Influenza A Virus, H7N9 Subtype - pathogenicity Influenza in Birds - virology Lung - pathology Lung - virology Macaca - virology Mice Neuraminidase - drug effects nonhuman primates Orthomyxoviridae Infections - pathology Orthomyxoviridae Infections - transmission Orthomyxoviridae Infections - virology pathogenicity receptor-binding specificity replication capacity Respiratory Tract Infections - pathology Respiratory Tract Infections - virology transmissibility Virus Replication |
| Title | A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets |
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