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

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


    Pathogens


    . 2020 Sep 2;9(9):E725.
    doi: 10.3390/pathogens9090725.
    In Vitro Characterization of Multidrug-Resistant Influenza A(H1N1)pdm09 Viruses Carrying a Dual Neuraminidase Mutation Isolated from Immunocompromised Patients


    Emi Takashita 1 , Seiichiro Fujisaki 1 , Masaru Yokoyama 2 , Masayuki Shirakura 1 , Hiroko Morita 1 , Kazuya Nakamura 1 , Noriko Kishida 1 , Tomoko Kuwahara 1 , Hironori Sato 2 , Ikuko Doi 3 , Yuji Sato 4 , Shinichi Takao 5 , Yukie Shimazu 5 , Takeshi Shimomura 6 , Takuo Ito 7 , Shinji Watanabe 1 , Takato Odagiri 1 , The Influenza Virus Surveillance Group Of Japan



    AffiliationsFree article

    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.

    Keywords: baloxavir; favipiravir; influenza; laninamivir; neuraminidase inhibitor; oseltamivir; peramivir; resistance; zanamivir.

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