tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Seiichiro Fujisaki[SUP] 1 [/SUP], Masaru Yokoyama[SUP] 2 [/SUP], Masayuki Shirakura[SUP] 1 [/SUP], Hiroko Morita[SUP] 1 [/SUP], Kazuya Nakamura[SUP] 1 [/SUP], Noriko Kishida[SUP] 1 [/SUP], Tomoko Kuwahara[SUP] 1 [/SUP], Hironori Sato[SUP] 2 [/SUP], Ikuko Doi[SUP] 3 [/SUP], Yuji Sato[SUP] 4 [/SUP], Shinichi Takao[SUP] 5 [/SUP], Yukie Shimazu[SUP] 5 [/SUP], Takeshi Shimomura[SUP] 6 [/SUP], Takuo Ito[SUP] 7 [/SUP], Shinji Watanabe[SUP] 1 [/SUP], Takato Odagiri[SUP] 1 [/SUP], The Influenza Virus Surveillance Group Of Japan
Affiliations
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.
. 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[SUP] 1 [/SUP], Seiichiro Fujisaki[SUP] 1 [/SUP], Masaru Yokoyama[SUP] 2 [/SUP], Masayuki Shirakura[SUP] 1 [/SUP], Hiroko Morita[SUP] 1 [/SUP], Kazuya Nakamura[SUP] 1 [/SUP], Noriko Kishida[SUP] 1 [/SUP], Tomoko Kuwahara[SUP] 1 [/SUP], Hironori Sato[SUP] 2 [/SUP], Ikuko Doi[SUP] 3 [/SUP], Yuji Sato[SUP] 4 [/SUP], Shinichi Takao[SUP] 5 [/SUP], Yukie Shimazu[SUP] 5 [/SUP], Takeshi Shimomura[SUP] 6 [/SUP], Takuo Ito[SUP] 7 [/SUP], Shinji Watanabe[SUP] 1 [/SUP], Takato Odagiri[SUP] 1 [/SUP], The Influenza Virus Surveillance Group Of Japan
Affiliations
- PMID: 32887429
- DOI: 10.3390/pathogens9090725
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.