Neuroinvasion of the Highly Pathogenic Influenza Virus H7N1 Is Caused by Disruption of the Blood Brain Barrier in an Avian Model
Visualitza/Obre
Autor/a
Chaves, Aida J.
Valle, Rosa
Rivas, Raquel
Data de publicació
2014-12-15ISSN
1932-6203
Resum
Influenza A virus (IAV) causes central nervous system (CNS) lesions in avian and mammalian species, including humans. However, the mechanism used by IAV to invade the brain has not been determined. In the current work, we used chickens infected with a highly pathogenic avian influenza (HPAI) virus as a model to elucidate the mechanism of entry of IAV into the brain. The permeability of the BBB was evaluated in fifteen-day-old H7N1-infected and non-infected chickens using three different methods: (i) detecting Evans blue (EB) extravasation into the brain, (ii) determining the leakage of the serum protein immunoglobulin Y (IgY) into the brain and (iii) assessing the stability of the tight-junction (TJ) proteins zonula occludens-1 and claudin-1 in the chicken brain at 6, 12, 18, 24, 36 and 48 hours post-inoculation (hpi). The onset of the induced viremia was evaluated by quantitative real time RT-PCR (RT-qPCR) at the same time points. Viral RNA was detected from 18 hpi onward in blood samples, whereas IAV antigen was detected at 24 hpi in brain tissue samples. EB and IgY extravasation and loss of integrity of the TJs associated with the presence of viral antigen was first observed at 36 and 48 hpi in the telencephalic pallium and cerebellum. Our data suggest that the mechanism of entry of the H7N1 HPAI into the brain includes infection of the endothelial cells at early stages (24 hpi) with subsequent disruption of the TJs of the BBB and leakage of virus and serum proteins into the adjacent neuroparenchyma.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
English
Matèries (CDU)
619 - Veterinària
Pàgines
25
Publicat per
Public Library of Science
Publicat a
PLoS ONE
Citació
Chaves, Aida J., Júlia Vergara-Alert, Núria Busquets, Rosa Valle, Raquel Rivas, Antonio Ramis, Ayub Darji, and Natàlia Majó. 2014. "Neuroinvasion Of The Highly Pathogenic Influenza Virus H7N1 Is Caused By Disruption Of The Blood Brain Barrier In An Avian Model". Plos ONE 9 (12): e115138. doi:10.1371/journal.pone.0115138.
Número de l'acord de la subvenció
EC/FP6/44098/EU/Molecular factors and mechanisms of transmission and pathogenicity of highly pathogenic Avian Influenza Virus/EUROFLU
Programa
Sanitat Animal
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