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2024-3-29 0:33:11


MARJUKI H, Mishin VP, Chesnokov AP, Jones J, et al. Characterization of Drug-Resistant Influenza A(H7N9) Variant Viruses Isolated from an Oseltamivir-Treated Patient in Taiwan. J Infect Dis. 2014 Aug 14.
submited by kickingbird at Aug, 25, 2014 7:22 AM from J Infect Dis. 2014 Aug 14.

BACKGROUND:

?Patients contracting influenza A(H7N9) often developed severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs) are the primary option for treatment, but information on drug-resistance markers for A(H7N9) is limited.

METHODS:

?Four NA variants of A/Taiwan/1/2013 (H7N9) virus containing a single substitution (NA-E119 V, NA-I222 K, NA-I222R or NA-R292 K), recovered from an oseltamivir-treated patient, were tested for NAI susceptibility in vitro; their replicative fitness was evaluated in cell culture, mice and ferrets.

RESULTS:

?NA-R292 K led to highly reduced inhibition by oseltamivir and peramivir, while NA-E119 V, NA-I222 K and NA-I222R caused reduced inhibition by oseltamivir. Mice infected with any virus showed severe clinical signs with high mortality rates. NA-I222 K virus was the most virulent in mice, whereas virus lacking NA change (NA-WT) and NA-R292 K virus seemed the least virulent. Sequence analysis suggests that PB2-S714N increased virulence of the NA-I222 K virus in mice; NS1-K126R, alone or in combination with PB2-V227M, produced contrasting effects in NA-WT and NA-R292 K viruses. In ferrets, all viruses replicated to high titers in the upper respiratory tract, but produced only mild illness. NA-R292 K virus, showed reduced replicative fitness in this animal model.

CONCLUSIONS:

?Our data highlight challenges in assessment of replicative fitness of H7N9 NA variants emerged in NAI-treated patients.

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