Neuroinvasion of the Highly Pathogenic Influenza Virus H7N1 Is Caused by Disruption of the Blood Brain Barrier in an Avian Model
Chaves Hernández, Aida Jeannette (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Vergara-Alert, Júlia (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Busquets, Núria (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Valle, Rosa (Institut de Recerca i Tecnologia Agroalimentàries)
Rivas, Raquel (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Ramis Salva, Antonio José (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Darji, Ayub (Institut de Recerca i Tecnologia Agroalimentàries)
Majó i Masferrer, Natàlia (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)

Data:	2015
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.
Nota:	Altres ajuts: EUROFLU/5B-CT-2007/044098
Nota:	Altres ajuts: E07D400404CR
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Antibodies ; Cell staining ; Central nervous system ; Cerebellum ; Chicken models ; Chickens ; Endothelial cells ; Influenza A virus
Publicat a:	PloS one, Vol. 9, Issue 12 (December 2014) , p.e115138, ISSN 1932-6203

DOI: 10.1371/journal.pone.0115138
PMID: 25506836

25 p, 14.4 MB

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