Immunohistochemical Demonstration of Equine Herpesvirus-1 Antigen in Neurons and Astrocytes of Horses with Acute Paralysis

Schultheiss, Patricia C.; Collins, James K.; Hotaling, S. F.

doi:10.1177/030098589703400110

Cited by 22 publications

(15 citation statements)

References 13 publications

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“…The characteristic lesions in horses infected with EHM are vasculitis of small vessels and thrombosis, resulting in ischaemic damage to the CNS. Although EHV-1 is not considered primarily neurotropic, it has been reported that the virus can induce lesions in neurons and astrocytes (12). Moreover, the present study found positive samples from the CNS or CSF by virus isolation and PCR.…”

Section: Case Reportsupporting

confidence: 54%

First detection of the equine herpesvirus 1 neuropathogenic variant in Brazil

Mori

Borges²,

Delfiol³

et al. 2011

Rev. Sci. Tech. OIE

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SummaryThis report describes the first detection of an equine herpesvirus 1 (EHV-1) neuropathogenic variant (G 2254 /D 752 ) in Brazil from a case of fatal equine herpesvirus myeloencephalopathy (EHM) in a mare. The results of nucleotide sequencing of the EHV-1 ORF30 gene showed that two other Brazilian EHV-1 isolates from EHM cases are representatives of the non-neuropathogenic variant (A 2254 /N 752 ), suggesting that other unidentified factors are probably also involved in the neuropathogenicity of EHV-1 in horses. These findings will contribute to the epidemiological knowledge of EHV-1 infection in Brazil. KeywordsBrazil -DNA polymerase gene -Equine herpesvirus 1 -Neurological diseaseNeuropathogenic.Equine herpesvirus type 1 (EHV-1) is an important and ubiquitous pathogen, which causes extensive economic losses in the horse industry. The virus induces respiratory disease in young horses, abortion in pregnant mares, perinatal foal mortality, and neurological disease. Infection may involve a single animal or an entire herd (8, 11).In recent years, the occurrence of equine herpesvirus myeloencephalopathy (EHM) among horse populations in North America and Europe has increased both in frequency and severity, leading the United States Department of Agriculture to designate EHM as an emerging infectious disease (2). Nugent et al. (9) showed that a single nucleotide polymorphism within the gene encoding the catalytic subunit of EHV-1 DNA polymerase (ORF30) is associated with clinical cases of EHM. The substitution of adenine (A) for guanine (G) at position 2,254 (A 2254 to G 2254 ) causes a replacement of asparagine (N) by aspartic acid (D) at amino acid position 752 (N 752 to D 752 ). During the leukocyte-associated viraemia that follows EHV-1 infections in horses, the neuropathogenic variant (G 2254 /D 752 ) replicates at higher levels and for a longer duration than the nonneuropathogenic variant (A 2254 /N 752 ) (1). However, the mechanism by which this leukocyte-associated viraemia leads to EHM, and when, is not yet understood. Although the first isolation of EHV-1 (from an equine aborted fetus) was recorded in Brazil in 1966, the first EHM case report occurred only in 2005. This fatal EHM case was of a single mare, housed in an equestrian facility (7).Recent studies using real-time polymerase chain reaction (PCR) showed that 7% (4/54) of the EHV-1 strains isolated in Argentina from abortion outbreaks were associated with the neuropathogenic variant (G 2254 /D 752 ), and only two of those four cases were associated with simultaneous neurological disease (15). The ORF30 genotyping of Brazilian EHV-1 isolates derived from abortions or neurological cases has not been reported. This paper is a report of three EHM cases, including the first reported neuropathogenic (G 2254 /D 752 ) EHV-1 isolate from Brazil.Brain tissues were fixed in 10% formalin, processed routinely, embedded in paraffin, sectioned at 5 µm thickness, and stained with haematoxylin and eosin (HE).Virus isolation was attempted with clinical samples (...

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Section: Case Reportsupporting

confidence: 54%

First detection of the equine herpesvirus 1 neuropathogenic variant in Brazil

Mori

Borges²,

Delfiol³

et al. 2011

Rev. Sci. Tech. OIE

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show abstract

“…In the natural host, following the primary respiratory involvement, the infection of the vascular endothelium with consecutive vasculitis and perivascular ischaemia govern the pathological events. Even in the brain the vascular pathology stands in the foreground, whereas direct virus attack on neurons is exceptional (11–13) or even absent (17). In the mouse, EHV‐1 is endotheliotropic only in extraneural organs, as shown by the presence of vasculitis, and virus antigen expression of vascular endothelia in the lung in our experiments, furthermore, by the occurrence of abortions in virus‐infected pregnant animals, as observed by others (18, 25, 56, 57).…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of equine herpesvirus‐1 infection in the mouse model

Gosztonyi

Borchers

Ludwig

2009

APMIS

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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.

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“…In contrast to other neuropathogenic alphaherpesviruses, which cause encephalitis via neuronal infection, EHV-1-induced myeloencephalopathy is caused by infection of vascular endothelia of arteries supplying the central nervous system (CNS). The subsequent inflammatory response leads to thrombosis and ischemic damage [5,6]. A sustained and high-level presence of viral DNA in the blood stream, and, by implication, cell-associated viremia, is associated with the development of neurologic disease in EHV-1-infected horses [7,8].…”

Section: Introductionmentioning

confidence: 99%

A Point Mutation in a Herpesvirus Polymerase Determines Neuropathogenicity

et al. 2007

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Infection with equid herpesvirus type 1 (EHV-1) leads to respiratory disease, abortion, and neurologic disorders in horses. Molecular epidemiology studies have demonstrated that a single nucleotide polymorphism resulting in an amino acid variation of the EHV-1 DNA polymerase (N752/D752) is significantly associated with the neuropathogenic potential of naturally occurring strains. To test the hypothesis that this single amino acid exchange by itself influences neuropathogenicity, we generated recombinant viruses with differing polymerase sequences. Here we show that the N752 mutant virus caused no neurologic signs in the natural host, while the D752 virus was able to cause inflammation of the central nervous system and ataxia. Neurologic disease induced by the D752 virus was concomitant with significantly increased levels of viremia (p = 0.01), but the magnitude of virus shedding from the nasal mucosa was similar between the N752 and D752 viruses. Both viruses replicated with similar kinetics in fibroblasts and epithelial cells, but exhibited differences in leukocyte tropism. Last, we observed a significant increase (p < 0.001) in sensitivity of the N752 mutant to aphidicolin, a drug targeting the viral polymerase. Our results demonstrate that a single amino acid variation in a herpesvirus enzyme can influence neuropathogenic potential without having a major effect on virus shedding from infected animals, which is important for horizontal spread in a population. This observation is very interesting from an evolutionary standpoint and is consistent with data indicating that the N752 DNA pol genotype is predominant in the EHV-1 population, suggesting that decreased viral pathogenicity in the natural host might not be at the expense of less efficient inter-individual transmission.

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Immunohistochemical Demonstration of Equine Herpesvirus-1 Antigen in Neurons and Astrocytes of Horses with Acute Paralysis

Cited by 22 publications

References 13 publications

First detection of the equine herpesvirus 1 neuropathogenic variant in Brazil

First detection of the equine herpesvirus 1 neuropathogenic variant in Brazil

Pathogenesis of equine herpesvirus‐1 infection in the mouse model

A Point Mutation in a Herpesvirus Polymerase Determines Neuropathogenicity

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