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Susceptibility of Brazilian influenza A(H1N1)pdm09 viruses to neuraminidase inhibitors in the 2014-2016 seasons: Identification of strains bearing mutations associated with reduced inhibition profile.
- Source :
-
Antiviral research [Antiviral Res] 2018 Jun; Vol. 154, pp. 35-43. Date of Electronic Publication: 2018 Mar 28. - Publication Year :
- 2018
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Abstract
- Neuraminidase inhibitors (NAIs) are the main class of antivirals currently used for the treatment of influenza infections. As influenza viruses are constantly evolving, drug-resistance can emerge resulting in reduced effectiveness of treatment. This study evaluated the presence of molecular markers associated with NAI susceptibility in 724 influenza A(H1N1)pdm09 positive samples from Brazilian surveillance system from the 2014-2016 seasons, including 76 isolates tested for oseltamivir (OST) susceptibility and 23 isolates also tested for zanamivir, peramivir and laninamivir susceptibility. We identified the H275Y (n = 3) and I223K (n = 1) NA substitutions, associated with reduced inhibition (RI) by the NAIs. Noteworthy, no epidemiological links were identified among the patients infected with the mutant viruses. Phylogenetic analysis from NA and hemagglutinin genes showed that mutant viruses were not clustered. All mutant virus strains carried the permissive substitutions V241I and N369K, in addition to the N386K, which has been shown to destabilize the NA structure. Functional NA analysis of one virus containing the H275Y mutation confirmed its highly RI profile to OST and peramivir and demonstrated that it had decreased viral replication and NA thermostability compared to the wild type virus. The remaining tested isolates presented normal inhibition profile to the NAIs tested. In conclusion, the overall frequency of influenza A(H1N1)pdm09 viruses bearing mutations associated with NAI RI was 0.6%, similar to what has been observed in recent global studies.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Child
Child, Preschool
Epidemiological Monitoring
Female
Hemagglutinin Glycoproteins, Influenza Virus genetics
Humans
Infant
Infant, Newborn
Influenza, Human drug therapy
Influenza, Human epidemiology
Male
Middle Aged
Mutation
Neuraminidase genetics
Virus Replication drug effects
Young Adult
Antiviral Agents pharmacology
Drug Resistance, Viral genetics
Enzyme Inhibitors pharmacology
Influenza A Virus, H1N1 Subtype drug effects
Influenza A Virus, H1N1 Subtype genetics
Neuraminidase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9096
- Volume :
- 154
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 29601892
- Full Text :
- https://doi.org/10.1016/j.antiviral.2018.03.010