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

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):725. doi: 10.3390/pathogens9090725.
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
Affiliations

Affiliations

  • 1 Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • 2 Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • 3 Ibaraki Prefectural Institute of Public Health, Ibaraki 310-0852, Japan.
  • 4 Tsukuba Memorial Hospital, Ibaraki 300-2622, Japan.
  • 5 Hiroshima Prefectural Technology Research Institute, Hiroshima 734-0007, Japan.
  • 6 National Hospital Organization Hiroshimanishi Medical Center, Hiroshima 739-0696, Japan.
  • 7 National Hospital Organization Kure Medical Center, Hiroshima 737-0023, Japan.
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.

Figures
Products