title: Neuropathogenesis of a highly pathogenic avian influenza virus (H7N1) in experimentally infected chickens.
abstract: In order to understand the mechanism of neuroinvasion of a highly pathogenic avian influenza virus (HPAIV) into the central nervous system (CNS) of chickens, specific pathogen free chickens were inoculated with a H7N1 HPAIV. Blood, cerebrospinal fluid (CSF), nasal cavity and brain tissue samples were obtained from 1 to 4 days post-inoculation (dpi) of infected and control chickens. Viral antigen topographical distribution, presence of influenza A virus receptors in the brain, as well as, the role of the olfactory route in virus CNS invasion were studied using different immunohistochemistry techniques. Besides, viral RNA load in CSF and blood was quantified by means of a quantitative real-time reverse transcription-polymerase chain reaction. Viral antigen was observed widely distributed in the CNS, showing bilateral and symmetrical distribution in the nuclei of the diencephalon, mesencephalon and rhombencephalon. Viral RNA was detected in blood and CSF at one dpi, indicating that the virus crosses the blood-CSF-barrier early during infection. This early dissemination is possibly favoured by the presence of Siaα2,3 Gal and Siaα2,6 Gal receptors in brain vascular endothelial cells, and Siaα2,3 Gal receptors in ependymal and choroid plexus cells. No viral antigen was observed in olfactory sensory neurons, while the olfactory bulb showed only weak staining, suggesting that the virus did not use this pathway to enter into the brain. The sequence of virus appearance and the topographical distribution of this H7N1 HPAIV indicate that the viral entry occurs via the haematogenous route, with early and generalized spreading through the CSF.
authors: Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. natalia.majo@cresa.uab.es.
authors: Aida J
authors: AJ
authors: Chaves
authors: Núria
authors: N
authors: Busquets
authors: Rosa
authors: R
authors: Valle
authors: Raquel
authors: R
authors: Rivas
authors: Júlia
authors: J
authors: Vergara-Alert
authors: Roser
authors: R
authors: Dolz
authors: Antonio
authors: A
authors: Ramis
authors: Ayub
authors: A
authors: Darji
authors: Natàlia
authors: N
authors: Majó
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D001921:Brain / Q000821:virology; D002490:Central Nervous System / Q000821:virology*; D002645:Chickens; D007150:Immunohistochemistry / Q000662:veterinary; D057916:Influenza A Virus, H7N1 Subtype / Q000502:physiology*; D005585:Influenza in Birds / Q000821:virology*; D037102:Lectins / Q000378:metabolism; D009832:Olfactory Nerve / Q000821:virology; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011201:Poultry Diseases / Q000821:virology*; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D013047:Specific Pathogen-Free Organisms; D019562:Viral Load / Q000662:veterinary; D056189:Viral Tropism
chemical_list: D000956:Antigens, Viral; D037102:Lectins; D012367:RNA, Viral