Differential viral-host immune interactions associated with oseltamivir-resistant H275Y and wild-type H1N1 A(pdm09) influenza virus pathogenicity
Visualitza/Obre
Autor/a
Vidaña, Beatriz
Martínez-Orellana, Pamela
Martorell, Jaime M.
Baratelli, Massimiliano
Migura-Garcia, Lourdes
Córdoba, Lorena
Pérez, Mónica
Casas, Inmaculada
Pozo, Francisco
Fraile, Lorenzo
Majó, Natàlia
Montoya, María
Data de publicació
2020-07-24ISSN
1999-4915
Resum
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.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
English
Matèries (CDU)
619 - Veterinària
Pàgines
20
Publicat per
MDPI
Publicat a
Viruses
Citació
Vidaña, Beatriz, Pamela Martínez-Orellana, Jaime Martorell, Massimiliano Baratelli, Jorge Martínez, Lourdes Migura-Garcia, and Lorena Córdoba et al. 2020. "Differential Viral-Host Immune Interactions Associated With Oseltamivir-Resistant H275Y And Wild-Type H1N1 A(Pdm09) Influenza Virus Pathogenicity". Viruses 12 (8): 794. doi:10.3390/v12080794.
Número de l'acord de la subvenció
INIA/Programa Nacional de Proyectos de Investigación Fundamental/RTA2011‐00111‐C03-01/ES/Avian influenza: relationship between the host, the pathogen and the ecosystem/
Programa
Sanitat Animal
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