tetano
Editor, Senior Moderator
J Infect Dis. 2014 Jun 20. pii: jiu353. [Epub ahead of print]
The R292 K mutation that confers resistance to neuraminidase inhibitors leads to competitive fitness loss of A/Shanghai/1/2013 (H7N9) influenza virus in ferrets.
Yen HL1, Zhou J2, Choy KT2, Sia SF2, Teng O2, Ng IH2, Fang VJ2, Hu Y3, Wang W3, Cowling BJ2, Nicholls JM4, Guan Y2, Peiris JS1.
Author information
Abstract
BACKGROUND:
The neuraminidase (NA) inhibitors are the only licensed therapeutic option for human zoonotic H7N9 infections. An NA-R292 K mutation that confers broad-spectrum resistance to NA inhibitors has been documented in H7N9 patients after treatment.
METHODS:
We evaluated the transmission potential of a human influenza A H7N9 isolate with a NA-R292 K mutation in the ferret model followed by genotyping assay to monitor its competitive fitness in vivo.
RESULTS:
Plaque-purified A/Shanghai/1/2013 wild-type and NA-R292 K viruses transmitted at comparable efficiency to direct or respiratory droplet contact ferrets. In ferrets inoculated with the plaque-purified A/Shanghai/1/2013 NA-R292 K virus with dominant K292 (94%), the resistant K292 genotype was outgrown by the wild-type R292 genotype during the course of infection. Transmission of the resistant K292 genotype was detected in 3/4 direct contact and 3/4 respiratory droplet contact ferrets at early time points but was gradually replaced by the wild-type genotype. In the respiratory tissues of inoculated or infected ferrets, the wild-type R292 genotype dominated in the nasal turbinate while the resistant K292 genotype was more frequently detected in the lungs.
CONCLUSIONS:
The NA inhibitor-resistant H7N9 virus with the NA-R292 K mutation may transmit among ferrets but showed compromised fitness in vivo while in competition with the wild-type virus.
? 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:
24951824
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24951824
The R292 K mutation that confers resistance to neuraminidase inhibitors leads to competitive fitness loss of A/Shanghai/1/2013 (H7N9) influenza virus in ferrets.
Yen HL1, Zhou J2, Choy KT2, Sia SF2, Teng O2, Ng IH2, Fang VJ2, Hu Y3, Wang W3, Cowling BJ2, Nicholls JM4, Guan Y2, Peiris JS1.
Author information
Abstract
BACKGROUND:
The neuraminidase (NA) inhibitors are the only licensed therapeutic option for human zoonotic H7N9 infections. An NA-R292 K mutation that confers broad-spectrum resistance to NA inhibitors has been documented in H7N9 patients after treatment.
METHODS:
We evaluated the transmission potential of a human influenza A H7N9 isolate with a NA-R292 K mutation in the ferret model followed by genotyping assay to monitor its competitive fitness in vivo.
RESULTS:
Plaque-purified A/Shanghai/1/2013 wild-type and NA-R292 K viruses transmitted at comparable efficiency to direct or respiratory droplet contact ferrets. In ferrets inoculated with the plaque-purified A/Shanghai/1/2013 NA-R292 K virus with dominant K292 (94%), the resistant K292 genotype was outgrown by the wild-type R292 genotype during the course of infection. Transmission of the resistant K292 genotype was detected in 3/4 direct contact and 3/4 respiratory droplet contact ferrets at early time points but was gradually replaced by the wild-type genotype. In the respiratory tissues of inoculated or infected ferrets, the wild-type R292 genotype dominated in the nasal turbinate while the resistant K292 genotype was more frequently detected in the lungs.
CONCLUSIONS:
The NA inhibitor-resistant H7N9 virus with the NA-R292 K mutation may transmit among ferrets but showed compromised fitness in vivo while in competition with the wild-type virus.
? 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:
24951824
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24951824