• Mina Nakauchi, Emi Takashita, Seiichiro Fujisaki, Masayuki Shirakura, Rie Ogawa, Hiroko Morita, Hideka Miura, Shinji Saito, Shinji Watanabe, Takato Odagiri, and Tsutomu Kageyama.
• Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
• Influenza Other Respi Viruses. 2020 Jul 1; 14 (4): 436-443.

BackgroundThe novel cap-dependent endonuclease inhibitor baloxavir marboxil was approved in February 2018 for the treatment of influenza virus infection in Japan. In vitro studies have revealed that an I38T substitution in the polymerase acidic subunit (PA) is associated with reduced susceptibility of influenza viruses to baloxavir.ObjectivesDevelopment of a rapid and simple method for monitoring influenza A(H1N1)pdm09, A(H3N2), and B viruses possessing the I38T substitution in PA.MethodsThree assays were developed based on RNase H2-dependent PCR (rhPCR) and named A/H1pdm PA_I38T rhPCR, A/H3 PA_I38T rhPCR, and B PA_I38T rhPCR. The assays were evaluated using cDNAs synthesized from in vitro-transcribed PA gene RNA controls, RNAs purified from viruses isolated in the 2017/2018 and 2018/2019 influenza seasons, and RNAs purified from clinical specimens collected in the 2018/2019 influenza season.ResultsThe assays developed in this study accurately discriminated PA I38 and PA T38 with high sensitivity.ConclusionsOur assays should be considered a powerful tool for monitoring the emergence of baloxavir-resistant influenza viruses.© 2020 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

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