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Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir.
Medaglia, Chiara; Zwygart, Arnaud Charles-Antoine; Silva, Paulo Jacob; Constant, Samuel; Huang, Song; Stellacci, Francesco; Tapparel, Caroline.
Afiliação
  • Medaglia C; Department of Microbiology and Molecular Medicine, University of Geneva, 1206 Geneva, Switzerland.
  • Zwygart AC; Department of Microbiology and Molecular Medicine, University of Geneva, 1206 Geneva, Switzerland.
  • Silva PJ; Insitute of Materials, Ecole polytechnique fédérale de Lausanne, 1015 Lausanne, Switzerland.
  • Constant S; Epithelix Sas, 1228 Geneva, Switzerland.
  • Huang S; Epithelix Sas, 1228 Geneva, Switzerland.
  • Stellacci F; Insitute of Materials, Ecole polytechnique fédérale de Lausanne, 1015 Lausanne, Switzerland.
  • Tapparel C; Department of Microbiology and Molecular Medicine, University of Geneva, 1206 Geneva, Switzerland.
Microorganisms ; 9(6)2021 Jun 01.
Article em En | MEDLINE | ID: mdl-34205874
Influenza viruses are a leading cause of morbidity and mortality worldwide. These air-borne pathogens are able to cross the species barrier, leading to regular seasonal epidemics and sporadic pandemics. Influenza viruses also possess a high genetic variability, which allows for the acquisition of resistance mutations to antivirals. Combination therapies with two or more drugs targeting different mechanisms of viral replication have been considered an advantageous option to not only enhance the effectiveness of the individual treatments, but also reduce the likelihood of resistance emergence. Using an in vitro infection model, we assessed the barrier to viral resistance of a combination therapy with the neuraminidase inhibitor oseltamivir and human interferon lambda against the pandemic H1N1 A/Netherlands/602/2009 (H1N1pdm09) virus. We serially passaged the virus in a cell line derived from human bronchial epithelial cells in the presence or absence of increasing concentrations of oseltamivir alone or oseltamivir plus interferon lambda. While the treatment with oseltamivir alone quickly induced the emergence of antiviral resistance through a single mutation in the neuraminidase gene, the co-administration of interferon lambda delayed the emergence of drug-resistant influenza virus variants. Our results suggest a possible clinical application of interferon lambda in combination with oseltamivir to treat influenza.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Microorganisms Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Suíça País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Microorganisms Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Suíça País de publicação: Suíça