title: The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system.
abstract: The olfactory nerve consists mainly of olfactory receptor neurons and directly connects the nasal cavity with the central nervous system (CNS). Each olfactory receptor neuron projects a dendrite into the nasal cavity on the apical side, and on the basal side extends its axon through the cribriform plate into the olfactory bulb of the brain. Viruses that can use the olfactory nerve as a shortcut into the CNS include influenza A virus, herpesviruses, poliovirus, paramyxoviruses, vesicular stomatitis virus, rabies virus, parainfluenza virus, adenoviruses, Japanese encephalitis virus, West Nile virus, chikungunya virus, La Crosse virus, mouse hepatitis virus, and bunyaviruses. However, mechanisms of transport via the olfactory nerve and subsequent spread through the CNS are poorly understood. Proposed mechanisms are either infection of olfactory receptor neurons themselves or diffusion through channels formed by olfactory ensheathing cells. Subsequent virus spread through the CNS could occur by multiple mechanisms, including trans-synaptic transport and microfusion. Viral infection of the CNS can lead to damage from infection of nerve cells per se, from the immune response, or from a combination of both. Clinical consequences range from nervous dysfunction in the absence of histopathological changes to severe meningoencephalitis and neurodegenerative disease.
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Debby
authors.initials: D
authors.lastname: van Riel
authors.forename: Rob
authors.initials: R
authors.lastname: Verdijk
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
mesh_terms: D000818:Animals; D001706:Biopsy; D002450:Cell Communication; D020805:Central Nervous System Viral Diseases / Q000473:pathology / Q000635:transmission / Q000821:virology*; D004058:Diffusion; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D006801:Humans; D007251:Influenza, Human / Q000473:pathology / Q000635:transmission / Q000821:virology*; D009832:Olfactory Nerve / Q000473:pathology / Q000821:virology*; D009975:Orthomyxoviridae / Q000302:isolation & purification* / Q000472:pathogenicity; D057089:Pathology, Molecular / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D056189:Viral Tropism; D014773:Virology / Q000379:methods; D014774:Virulence
keywords: CNS; H5N1; cell-to-cell transmission; influenza; olfactory nerve; olfactory receptor neuron; virus