Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets

Nat Microbiol. 2020 Jan;5(1):27-33. doi: 10.1038/s41564-019-0609-0. Epub 2019 Nov 25.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cricetinae
  • Dibenzothiepins
  • Drug Resistance, Viral*
  • Ferrets
  • Humans
  • 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
  • Mice
  • Morpholines
  • Nasal Lavage Fluid / virology
  • Orthomyxoviridae Infections / transmission
  • Orthomyxoviridae Infections / virology
  • Oxazines / pharmacology*
  • Pyridines / pharmacology*
  • Pyridones
  • RNA-Dependent RNA Polymerase / genetics
  • Thiepins / pharmacology*
  • Triazines / pharmacology*
  • Viral Proteins / genetics
  • Virulence
  • Virus Replication

Substances

  • Antiviral Agents
  • Dibenzothiepins
  • Morpholines
  • Oxazines
  • PA protein, influenza viruses
  • Pyridines
  • Pyridones
  • Thiepins
  • Triazines
  • Viral Proteins
  • baloxavir
  • RNA-Dependent RNA Polymerase