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.

Pathobiology and transmission of highly and low pathogenic avian influenza viruses in European quail (Coturnix c. coturnix)

“…Interestingly, H5N1/HP showed a broader tissue distribution compared with H7N1/HP, suggesting that virus replication in a particular target organ other than respiratory or intestinal organs may contribute to the virulence of the HPAIV in quail, as previously stated [15]. Particularly, neurotropism is considered one of the main factors for the fatal course of AI in birds [45,46], evidenced in our study by the higher virulence of the H5N1/HP compared with H7N1/HP. Our findings in H7N2/LP correlate well with those of Makarova et al [16], in which a wide range of LPAIV subtypes could replicate efficiently in Japanese quail, predominantly in the respiratory tract.…”

Mechanism of West Nile Virus Neuroinvasion: A Critical Appraisal

“…Both studies have highlighted virus entry via this route is possible, either by a “Trojan horse” method [87] or a direct involvement with cell surface receptors of the choroid plexus epithelial cells [88]. For WNV, one research group has suggested the involvement of this barrier [57,70].…”

Neuroglia in Infectious Brain Diseases

“…Their roles in response to infection have not been well studied, although they presumably do participate, particularly with regards to the BCB dysfunction that can occur as part of the pathology in many CNS inflammatory states. They have been demonstrated to be a target of infection, as with influenza viruses and malaria (Chaves et al, 2011;Rivera Fernandez et al, 2015). They have been demonstrated to be a target of infection, as with influenza viruses and malaria (Chaves et al, 2011;Rivera Fernandez et al, 2015).…”