A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets.

Masaki Imai1 Tokiko Watanabe2 Maki Kiso2 Noriko Nakajima3 Seiya Yamayoshi2 Kiyoko Iwatsuki-Horimoto2 Masato Hatta4 Shinya Yamada2 Mutsumi Ito2 Yuko Sakai-Tagawa2 Masayuki Shirakura5 Emi Takashita5 Seiichiro Fujisaki5 Ryan McBride6 Andrew J Thompson6 Kenta Takahashi3 Tadashi Maemura2 Hiromichi Mitake2 Shiho Chiba4 Gongxun Zhong4 Shufang Fan4 Kohei Oishi2 Atsuhiro Yasuhara2 Kosuke Takada2 Tomomi Nakao2 Satoshi Fukuyama2 Makoto Yamashita2 Tiago J S Lopes7,4 Gabriele Neumann4 Takato Odagiri5 Shinji Watanabe5 Yuelong Shu8 James C Paulson6 Hideki Hasegawa3 Yoshihiro Kawaoka7,9,10
Affiliations 10 institutions
  1. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. Electronic address: [email protected].
  2. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
  3. Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
  4. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
  5. Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan.
  6. Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  7. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
  8. National Institute for Viral Disease Control and Prevention, China Centers for Disease Control and Prevention, Beijing 102206, China.
  9. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA
  10. Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. Electronic address: [email protected].

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.

Supporting text Virus Host Location
antiviral sensitivity 1 ferrets 79 highly pathogenic avian influenza H7N9 viruses 1 mice 254 nonhuman primates 3 pathogenicity 54 receptor-binding specificity 3 replication capacity 1 transmissibility 13 Animals 1948 Antiviral Agents 21 Brain 13 Cell Line 158 Chickens 146 Conjunctiva 2 Disease Models, Animal 77 Enzyme Inhibitors 3 Ferrets 79 Humans 1440 Influenza A Virus, H7N9 Subtype 87 Influenza in Birds 341 Lung 65 Macaca 6 Mice 253

Evidence records

5 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type
1 records
OVE2746
Key finding

A highly pathogenic avian H7N9 influenza virus was successfully isolated from a human clinical case.

Virus
Host
Location
Not specified
Supporting text

A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets.

Sample type
clinical sample
Experimental Infection
4 records · 2 evidence types
Evidence type
3 records
OVE2749
Key finding

The neuraminidase-sensitive variant of the highly pathogenic H7N9 virus caused death in experimentally infected and exposed ferrets.

Virus
Host
Location
Not specified
Supporting text

All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals.

Method
respiratory droplet infection | mortality observation
Experimental system
ferret respiratory droplet infection model
OVE2747
Key finding

Highly pathogenic H7N9 viruses were more pathogenic in mice than the low pathogenic H7N9 virus in controlled infections.

Virus
Host
Location
Not specified
Supporting text

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.

Method
controlled animal infection | viral replication assays | clinical observation
Experimental system
mouse infection model
OVE2748
Key finding

Highly pathogenic H7N9 viruses were more pathogenic in ferrets than the low pathogenic H7N9 virus in experimental infections.

Virus
Host
Location
Not specified
Supporting text

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.

Method
controlled animal infection | viral replication assays | clinical observation
Experimental system
ferret infection model
Evidence type
1 records
OVE2750
Key finding

H7N9 influenza viruses were transmitted among ferrets via respiratory droplets in an experimental setup.

Virus
Host
Location
Not specified
Supporting text

All viruses transmitted among ferrets via respiratory droplets.

Method
ferret aerosol/contact transmission experiment | virological monitoring of recipient animals
Experimental system
respiratory droplet transmission model in ferrets