tetano
Editor, Senior Moderator
J Infect Dis. 2014 Aug 14. pii: jiu447. [Epub ahead of print]
Characterization of Drug-Resistant Influenza A(H7N9) Variant Viruses Isolated from an Oseltamivir-Treated Patient in Taiwan.
Marjuki H1, Mishin VP1, Chesnokov AP2, Jones J1, De La Cruz JA2, Sleeman K1, Tamura D3, Nguyen HT2, Wu HS4, Chang FY4, Liu MT4, Fry AM1, Cox NJ1, Villanueva JM1, Davis CT1, Gubareva LV5.
Author information
Abstract
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.
? The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID:
25124927
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25124927
Characterization of Drug-Resistant Influenza A(H7N9) Variant Viruses Isolated from an Oseltamivir-Treated Patient in Taiwan.
Marjuki H1, Mishin VP1, Chesnokov AP2, Jones J1, De La Cruz JA2, Sleeman K1, Tamura D3, Nguyen HT2, Wu HS4, Chang FY4, Liu MT4, Fry AM1, Cox NJ1, Villanueva JM1, Davis CT1, Gubareva LV5.
Author information
Abstract
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.
? The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID:
25124927
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25124927