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Title:
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Differential viral-host immune interactions associated with Oseltamivir-resistant H275Y and wild type H1N1 A(pdm09) Influenza virus pathogenicity
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Author:
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Vidaña, Beatriz; Martinez-Orellana, Pamela; Martorell, Jaume; Baratelli, Massimiliano; Martínez, Jorge; García-Migura, Lourdes; Cordoba, Lorena; Pérez, Mónica; Casas, Inmaculada; Pozo, Francisco; Fraile Sauce, Lorenzo José; Majó, Natalia; Montoya, Maria
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Notes:
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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.
This work was funded by the coordinated project RTA 2011-00111-C03 of the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), by Instituto de Salud Carlos III (“Programa especial de investigación sobre la gripe pandémica” GR09/0023, GR09/0040, GR09/0039), and by the Servei de Diagnòstic de Patologia Veterinària (SDPV) of the Universitat Autònoma de Barcelona. This work was also partially funded by the CERCA program from Generalitat de Catalunya. |
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Subject(s):
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-Influenza
-Immunopathology
-Pneumonia
-Resistance
-Oseltamivir |
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Rights:
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cc-by (c) Vidaña, Beatriz et al., 2020
http://creativecommons.org/licenses/by/4.0/
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Document type:
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Article
Article - Published version |
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Published by:
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MDPI
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