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...

Full description

Saved in:
Bibliographic Details
Published in:Pathogens (Basel) 2020-09, Vol.9 (9), p.725
Main Authors: 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, on behalf of The Influenza Virus Surveillance Group of Japan
Format: Article
Language:English
Subjects:
Adsorption
Cross-resistance
Exo-a-sialidase
Genomics
Immunocompromised hosts
Infections
Influenza
Influenza A
laninamivir
Life sciences
Multidrug resistance
Mutants
Mutation
neuraminidase inhibitor
Oseltamivir
Patients
peramivir
Proteins
Public health
RNA polymerase
Substitutes
Viruses
Zanamivir
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2076-0817
2076-0817
DOI:10.3390/pathogens9090725