Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: Equine stroke

Abstract

Eight mares were infected with equid herpesvirus-1 subtype 1 isolated from a case of equine paresis. In two mares killed at 4 d.p.i. immunofluorescence showed endothelial cell infection together with thrombosis in the rete arteriosus of the nasal mucosa and also in the spinal cord of one of these mares. Circulating platelet counts in the other six mares fell as early as 2 d.p.i. and remained depressed for seven days. Circulating immune complexes started to appear at 2 d.p.i., reached maximum levels at 10 d.p.i., but were undetectable at 28 d.p.i. Three of the six remaining mares developed varying degrees of inco-ordination at 8 and 9 d.p.i. In the two inco-ordinate mares that were killed at 9 and 10 d.p.i. the haemorrhages in the spinal cord and brain were associated with extensive endothelial cell fluorescence and thrombus formation. Clinical paresis coincided with an increase in circulating complement fixing and neutralising antibodies which in all six mares were higher against the subtype 2 isolate than subtype 1. In five yearlings infected with a subtype 2 isolate of EHV-1 platelet counts remained normal and neither immune complexes nor viraemia, nor inco-ordination were detected.

Pathogenicity of a New Neurotropic Equine Herpesvirus 9(Gazelle Herpesvirus 1) in Horses.

“…Therefore EHV-9 will possess pathogenicity in the horse. The clinical symptoms and antibody responses of EHV-9 inoculated horses were almost identical to primary EHV-1 infection of horses with EHV-4 anamnestic infection [9]. The antibody response of H1 and H2 indicated that both of the horses had experience of previous infection with EHV-4.…”

“…The histopathological changes caused by EHV-9 were partially resembled to those of EHV-1 infected horses showing paresis [1,3,9,12,13,23]. Common features between EHV-9 encephalitis and EHV-1-associated meningoencephalomyelitis were cellular reaction including perivascular cuffing and glial reaction.…”

In vitro reactivation of latent equid herpesvirus-1 from CD5+/CD8+ leukocytes indirectly by IL-2 or chorionic gonadotrophin.

“…However, eCG was not mitogenic and its ability to reactivate was independent of IL-2 mediation. The persistence of latent EHV-1 in T lymphocytes and its reactivation by eCG is consistent with EHV-1 infecting the endothelial lining of the endometrium in pregnant mares (Edington et al, 1986 ;Smith et al, 1992), particularly when abortion has occurred weeks or months after detectable viraemia (Gleeson & Collins, 1980). The evidence from culturing separate leukocyte populations indicates that both IL-2 and eCG reactivated EHV-1 indirectly.…”

“…During the viraemia EHV-1 has been isolated for up to 3 weeks postinfection from peripheral blood mononuclear cells, predominantly from T lymphocytes and to a lesser extent monocytes (Bumgardner et al, 1982 ;Kydd et al, 1994). This cell-associated viraemia in an acute infection has been shown to be a prerequisite for abortion and paresis by initiating replication of EHV-1 in endothelial cells in the pregnant uterus and CNS (Patel et al, 1982 ;Edington et al, 1986Edington et al, , 1991.…”

Genetic diversity of equine herpesvirus 1 isolated from neurological, abortigenic and respiratory disease outbreaks

“…Numerous studies have demonstrated that differences in pathogenicity correlate with the ability to disseminate to and infect vascular endothelial cells in the uterus and central nervous system (Edington, Bridges, & Patel, 1986; Mumford et al., 1994; Patel, Edington, & Mumford, 1982; Platt, Singh, & Whitwell, 1980). Viruses carrying the A2254G neurological marker are thought to replicate to a higher level and induce a longer‐lasting viraemia than those lacking it (Allen & Breathnach, 2006).…”