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

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 cros...

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Detalles Bibliográficos
Autores principales: Takashita, Emi, Fujisaki, Seiichiro, Yokoyama, Masaru, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559125/
https://www.ncbi.nlm.nih.gov/pubmed/32887429
http://dx.doi.org/10.3390/pathogens9090725
Descripción
Sumario: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.

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