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

Cell Host Microbe. 2017 Nov 8;22(5):615-626.e8. doi: 10.1016/j.chom.2017.09.008. Epub 2017 Oct 19.

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.

Keywords: antiviral sensitivity; ferrets; highly pathogenic avian influenza H7N9 viruses; mice; nonhuman primates; pathogenicity; receptor-binding specificity; replication capacity; transmissibility.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Brain / pathology
  • Brain / virology
  • Cell Line
  • Chickens / virology
  • Conjunctiva / pathology
  • Conjunctiva / virology
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Ferrets / virology*
  • 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
  • Orthomyxoviridae Infections / pathology*
  • Orthomyxoviridae Infections / transmission*
  • Orthomyxoviridae Infections / virology*
  • Respiratory Tract Infections / pathology
  • Respiratory Tract Infections / virology
  • Virus Replication

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Neuraminidase