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.

Molecular detection of equine herpes virus-1 in local horses (Equus feruscaballus) and donkeys (Equus asinus

“…No viral DNA was detected at 7 to 11days PI. Mouse tissues collected from control animals didn't show any DNA PCR product, and they were negative for EHV-1 (Table, 2 In mice inoculated with male donkey samples, the virus followed the same sequence of antigen fate reported by many authors (14)(15)(16). This finding might indicate that the infection of such donkey has recently occurred or might be related to reactivation of the virus from past infection.…”

“…Thus these cells become important reservoirs for persistent viral infection (12 and 13). Mice were used as a potential animal model in experimental infections for this virus by many workers (14)(15)(16). Experimentally infected mice with EHV-1 produced clinical signs, like respiratory distress and weight loss (16 and 17).…”

Diverse Pathogenicity of Equine Herpesvirus 1 (EHV-1) Isolates in CBA Mouse Model

“…Gosztonyi et al [9] reported that EHV-1 behaved neurotropic in CNS of mice in contrasted with in horse. In the present study, vasculitis with perivascular mononuclear cuffing found in the brain of mice infected with 89c1, 90c18, 97c11, 98c12, 01c1, or Ab4p was consistent with the lesion found in the brain of natural EHV-1 infected horse from the outbreak of neurological disease [17].…”

Equine herpesvirus type 1 (EHV-1) replication in primary murine neurons culture

“…Mice genetically susceptible to EHV-1 infection (Awan et al 1990, Gosztonyi et al 2009) Balb/c (H-2d) were used to establish primary culture of murine neurons. Balb/c mice aged 6-8 weeks were purchased from the Centre for Experimental Medicine (Warsaw) and were treated in accordance with the guidelines regarding the use and care of laboratory animals.…”

“…Therefore, pathogenesis of EHV-1 infection and other phenomena associated with productive and latent infections mostly studied in animals models. An excellent model is the BALB/c mouse, because it has been demonstrated that EHV-1 infection in this mouse strains is similar to that of the natural host (Awan et al 1990, Walker et al 1999, Gosztonyi et al 2009). Accordingly, in the acute form, viremia developes, the virus replicates in the respiratory system and virus tropism to fetuses can be observed in pregnant females.…”