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Antimicrob Agents Chemother. 2014 Sep 22. pii: AAC.03667-14. [Epub ahead of print]
Multiple influenza A (H3N2) mutations conferring resistance to neuraminidase inhibitors in a bone marrow transplant recipient.
Eshaghi A1, Shalhoub S2, Rosenfeld P1, Li A1, Higgins RR1, Stogios PJ3, Savchenko A3, Bastien N4, Li Y4, Rotstein C2, Gubbay JB5.
Author information
Abstract
Immunocompromised patients are predisposed to infections caused by influenza. Influenza may produce considerable morbidity including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistance strains. Characterization of neuraminidase inhibitor (NAI) resistant strains of influenza A is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified a NAI resistant strain of influenza A (H3N2) in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance including transient R292K, Q136K and sustained E119K (N2 numbering) in neuraminidase (NA) protein emerged during prolonged antiviral therapy. In addition, a combination of a four amino acid deletion at residues 245 to 248 (Δ245-248) accompanied by E119V substitution occurred causing resistance to or reduced inhibition by neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir and peramivir). Resistant variants within a pool of viral quasispecies arose during combined antiviral treatment. More research is needed to understand the interplay of drug resistance mutations, viral fitness and transmission.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25246391
[PubMed - as supplied by publisher]
Multiple influenza A (H3N2) mutations conferring resistance to neuraminidase inhibitors in a bone marrow transplant recipient.
Eshaghi A1, Shalhoub S2, Rosenfeld P1, Li A1, Higgins RR1, Stogios PJ3, Savchenko A3, Bastien N4, Li Y4, Rotstein C2, Gubbay JB5.
Author information
Abstract
Immunocompromised patients are predisposed to infections caused by influenza. Influenza may produce considerable morbidity including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistance strains. Characterization of neuraminidase inhibitor (NAI) resistant strains of influenza A is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified a NAI resistant strain of influenza A (H3N2) in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance including transient R292K, Q136K and sustained E119K (N2 numbering) in neuraminidase (NA) protein emerged during prolonged antiviral therapy. In addition, a combination of a four amino acid deletion at residues 245 to 248 (Δ245-248) accompanied by E119V substitution occurred causing resistance to or reduced inhibition by neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir and peramivir). Resistant variants within a pool of viral quasispecies arose during combined antiviral treatment. More research is needed to understand the interplay of drug resistance mutations, viral fitness and transmission.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25246391
[PubMed - as supplied by publisher]
