In Vitro Characterization of Multidrug-Resistant Influenza A(H1N1)pdm09 Viruses Carrying a Dual Neuraminidase Mutation Isolated from Immunocompromised Patients

Author:

Takashita EmiORCID,Fujisaki Seiichiro,Yokoyama MasaruORCID,Shirakura Masayuki,Morita Hiroko,Nakamura Kazuya,Kishida Noriko,Kuwahara Tomoko,Sato Hironori,Doi Ikuko,Sato Yuji,Takao Shinichi,Shimazu Yukie,Shimomura Takeshi,Ito Takuo,Watanabe Shinji,Odagiri Takato,Surveillance Group of Japan on behalf of The Influenza Virus

Abstract

Influenza A(H1N1)pdm09 viruses carrying a dual neuraminidase (NA) substitution were isolated from immunocompromised patients after administration of one or more NA inhibitors. These mutant viruses possessed an H275Y/I223R, H275Y/I223K, or H275Y/G147R substitution in their NA and showed enhanced cross-resistance to oseltamivir and peramivir and reduced susceptibility to zanamivir compared to single H275Y mutant viruses. Baloxavir could be a treatment option against the multidrug-resistant viruses because these dual H275Y mutant viruses showed susceptibility to this drug. The G147R substitution appears to stabilize the NA structure, with the fitness of the H275Y/G147R mutant virus being similar or somewhat better than that of the wild-type virus. Since the multidrug-resistant viruses may be able to transmit between humans, surveillance of these viruses must continue to improve clinical management and to protect public health.

Publisher

MDPI AG

Subject

Infectious Diseases,Microbiology (medical),General Immunology and Microbiology,Molecular Biology,Immunology and Allergy

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