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Antiviral resistance due to deletion in the neuraminidase gene and defective interfering-like viral polymerase basic 2 RNA of influenza A virus subtype H3N2.
- Source :
-
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology [J Clin Virol] 2018 May; Vol. 102, pp. 1-6. Date of Electronic Publication: 2018 Feb 11. - Publication Year :
- 2018
-
Abstract
- Background and Objective: Antiviral treatment of influenza virus infections can lead to drug resistance of virus. This study investigates a selection of mutations in the full genome of H3N2 influenza A virus isolated from a patient in treatment with oseltamivir.<br />Study Design: Respiratory samples from a patient were collected before, during, and after antiviral treatment. Whole genome sequencing of the influenza virus by next generation sequencing, and low-frequency-variant analysis was performed. Neuraminidase-inhibition tests were performed with oseltamivir and zanamivir, and viruses were propagated in sial-transferase gene transfected Madin-Darby Canine Kidney cells.<br />Results: A deletion at amino acid position 245-248 in the neuraminidase gene occurred after initiation of treatment with oseltamivir. The deleted virus had highly reduced inhibition against oseltamivir but was sensitive to zanamivir. Nine days after discontinuation of oseltamivir treatment the deleted H3N2 virus was still present in the patient. After three passages of the deleted virus in cell culture, the deletion was retained. Several variant mutations appeared in the other genes of the H3N2 virus, where most striking were two major out-of-frame deletions in the polymerase basic 2 (PB2) gene, indicating defective interfering-like viral RNA.<br />Conclusions: The viruses harboring the 245-248 deletion in the neuraminidase gene were still present after discontinuation of oseltamivir treatment and passages in cell cultures, indicating a potential risk for transmission of the deleted virus. Full genome deep sequencing was useful to reveal variant mutations that might be selected due to antiviral treatment, and defective interfering-like viral PB2 RNA in the respiratory samples was detected.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Antiviral Agents pharmacology
Defective Viruses genetics
Defective Viruses isolation & purification
Denmark
Dogs
Humans
Influenza A Virus, H3N2 Subtype genetics
Influenza, Human virology
Madin Darby Canine Kidney Cells
Neuraminidase antagonists & inhibitors
Oseltamivir pharmacology
Oseltamivir therapeutic use
Respiratory System virology
Sequence Deletion
Treatment Outcome
Zanamivir pharmacology
Zanamivir therapeutic use
Antiviral Agents therapeutic use
Drug Resistance, Viral drug effects
Drug Resistance, Viral genetics
Influenza A Virus, H3N2 Subtype drug effects
Influenza, Human drug therapy
Neuraminidase genetics
RNA, Viral genetics
RNA-Dependent RNA Polymerase genetics
Viral Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5967
- Volume :
- 102
- Database :
- MEDLINE
- Journal :
- Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
- Publication Type :
- Academic Journal
- Accession number :
- 29448067
- Full Text :
- https://doi.org/10.1016/j.jcv.2018.02.005