title: Pathogenesis of equine herpesvirus-1 infection in the mouse model.
abstract: Equine herpesvirus-1 (EHV-1) is a major equine pathogen causing respiratory diseases, abortions and severe neurological disorders. The basis of neurological disturbances is, as in other organs, infection of endothelial cells, followed by vasculitis, thrombosis and ischaemic damage of the parenchyma. Here, a murine model was used to explore the mechanism of entry to, and spread within the brain, the cell affinity of the agent and the modulating role of the immune defence, which are all factors governing the pathogenesis of the neurological disease. Because controversial views exist about these mechanisms, we undertook a neuropathological study with intranasally infected adult mice. EHV-1 entered the brain through the olfactory neuroepithelium and along the olfactory nerves, and spread transsynaptically in rostro-caudal direction, using olfactory and limbic neuronal networks. Exclusively neurons were infected. The cellular immune reaction exerted a restraining effect on virus dissemination. Following nasal infection, the olfactory route was the major pathway for virus entry and dissemination, involvement of the trigeminal nerve in virus spread seems much less probable. In the adult mouse brain EHV-1 behaves as a typical neurotropic agent, using, similarly to other herpesviruses, the neuronal networks for dissemination. Vasculitis, the predominant type of lesion in natural infection, and endothelial cell positivity for EHV-1 were detectable only in the lung. Thus, this agent exhibits in the mouse a dual affinity: it is neurotropic in the brain, and endotheliotropic in visceral organs. Consideration of pathogenetic aspects of equine and experimental murine EHV-1 infections also helps a better understanding of human herpetic brain disease.
authors.affiliation: Institut für Neuropathologie, Charité, Universitätsmedizin Berlin, Berlin.
authors.forename: Georg
authors.initials: G
authors.lastname: Gosztonyi
authors.forename: Kerstin
authors.initials: K
authors.lastname: Borchers
authors.forename: Hanns
authors.initials: H
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000302:isolation & purification / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology / Q000821:virology; D006566:Herpesviridae Infections / Q000150:complications / Q000473:pathology / Q000821:virology*; D004861:Herpesvirus 1, Equid; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000473:pathology / Q000821:virology; D008590:Meningoencephalitis / Q000209:etiology / Q000473:pathology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000821:virology*; D009474:Neurons / Q000473:pathology / Q000821:virology*; D009833:Olfactory Pathways / Q000473:pathology / Q000821:virology; D014657:Vasculitis / Q000473:pathology
chemical_list: D000956:Antigens, Viral