Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity
Vidaña, Beatriz (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Martínez-Orellana, Pamela (International Centre for Genetic Engineering and Biotechnology . Laboratory of Molecular Virology)
Martorell Montserrat, Jaume (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals)
Baratelli, Massimiliano (HIPRA Laboratories)
Martínez Martínez, Jorge (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Migura-Garcia, Lourdes (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Córdoba, Lorena (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Pérez-Maíllo, Mónica (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Casas, Inmaculada (Centro Nacional de Microbiología (Espanya))
Pozo, Francisco (Centro Nacional de Microbiología (Espanya))
Fraile, Lorenzo (Universitat de Lleida. Departament de Ciència Animal)
Majó i Masferrer, Natàlia (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Montoya, Maria (Centro de Investigaciones Biológicas (Madrid))

Date:	2020
Abstract:	Oseltamivir is a common therapy against influenza A virus (IAV) infections. The acquisition of oseltamivir resistance (OR) mutations, such as H275Y, hampers viral fitness. However, OR H1N1 viruses have demonstrated the ability to spread throughout different populations. The objective of this work was to compare the fitness of two strains of OR (R6 and R7) containing the H275Y mutation, and a wild-type (F) pandemic influenza A (H1N1) 2009 (pdm09) virus both in vitro and in vivo in mice and to select one OR strain for a comparison with F in ferrets. R6 showed faster replication and pathogenicity than R7 in vitro and in mice. Subsequently, R6 was selected for the fitness comparison with the F strain in ferrets. Ferrets infected with the F virus showed more severe clinical signs, histopathological lung lesions, and viral quantification when compared to OR R6-infected animals. More importantly, differential viral kinetics correlated with differential pro-inflammatory host immune responses in the lungs of infected ferrets, where OR-infected animals developed a protective higher expression of type I IFN and Retinoid acid Inducible Gene I (RIG-I) genes early after infection, resulting in the development of milder disease. These results suggest the presence of early specific viral-host immune interactions relevant in the development of influenza-associated lung pathology.
Grants:	Instituto de Salud Carlos III GR09/0023 Instituto de Salud Carlos III GR09/0040 Instituto de Salud Carlos III GR09/0039
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Influenza ; Immunopathology ; Pneumonia ; Ph1n1 ; Resistance ; Oseltamivir
Published in:	Viruses, Vol. 12 (july 2020) , ISSN 1999-4915

DOI: 10.3390/v12080794
PMID: 32721992

20 p, 2.7 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Centre de Recerca en Sanitat Animal (CReSA-IRTA)
Articles > Research articles
Articles > Published articles