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Equine herpesvirus type 1(EHV-1)-associated myeloencephalopathy (EHM) is a rare disease affecting the central nervous system and, in particular, the spinal cord of horses. Epidemiologic data are limited, and usually are restricted to the description of a single outbreak. During an observational period of 4 years, we evaluated 9 outbreaks of EHM in The Netherlands. A risk factor analysis was done on the data from 6 outbreaks. Findings were: regular appearance of EHM outbreaks in The Netherlands (2-3/y); strong association of EHM with season; and risk factors, such as breed, sex, age, and fever. Female horses, aged horses, and specific breeds were at greater risk to develop severe neurologic disease. Other breeds and horses <3 years old were never observed to suffer from EHM during these outbreaks. It was concluded that breed variation, in addition to the presence of a specific EHV-1 strain, and environmental factors influence an outbreak of EHM on a premise.

Equine herpesvirus type 1(EHV-1)-associated myeloencephalopathy (EHM) is a rare disease affecting the central nervous system and, in particular, the spinal cord of horses. Epidemiologic data are limited, and usually are restricted to the description of a single outbreak. During an observational period of 4 years, we evaluated 9 outbreaks of EHM in The Netherlands. A risk factor analysis was done on the data from 6 outbreaks. Findings were: regular appearance of EHM outbreaks in The Netherlands (2-3/y); strong association of EHM with season; and risk factors, such as breed, sex, age, and fever. Female horses, aged horses, and specific breeds were at greater risk to develop severe neurologic disease. Other breeds and horses <3 years old were never observed to suffer from EHM during these outbreaks. It was concluded that breed variation, in addition to the presence of a specific EHV-1 strain, and environmental factors influence an outbreak of EHM on a premise.

After many years of controversy, there is now recent and solid evidence that classical Borna disease virus 1 (BoDV-1) can infect humans. On the basis of six brain autopsies, we provide the first systematic overview on BoDV-1 tissue distribution and the lesion pattern in fatal BoDV-1-induced encephalitis. All brains revealed a non-purulent, lymphocytic sclerosing panencephalomyelitis with detection of BoDV-1-typical eosinophilic, spherical intranuclear Joest–Degen inclusion bodies. While the composition of histopathological changes was constant, the inflammatory distribution pattern varied interindividually, affecting predominantly the basal nuclei in two patients, hippocampus in one patient, whereas two patients showed a more diffuse distribution. By immunohistochemistry and RNA in situ hybridization, BoDV-1 was detected in all examined brain tissue samples. Furthermore, infection of the peripheral nervous system was observed. This study aims at raising awareness to human bornavirus encephalitis as differential diagnosis in lymphocytic sclerosing panencephalomyelitis. A higher attention to human BoDV-1 infection by health professionals may likely increase the detection of more cases and foster a clearer picture of the disease.

Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EHV-1 (WT). Infection with either virus led to cytokine responses that coincided with the course of clinical disease, particularly the biphasic pyrexia, which correlates with respiratory disease and viremia, respectively. Similarly, both viruses caused suppression of proliferative T-cell responses on day 7 post infection (pi). The ΔORF1/ORF2 virus caused significantly shorter primary pyrexia and significantly reduced nasal shedding, and an attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared to WT-infected ponies. In conclusion, our findings are (i) that infection of ponies with EHV-1 leads to modulation of immune responses, which are correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of importance for disease outcome and modulation of cytokine responses.

Despite the importance of neurological disorders associated with herpesviruses, the mechanism by which these viruses influence the central nervous system (CNS) has not been definitively established. Owing to the limitations of studying neuropathogenicity of human herpesviruses in their natural host, many aspects of their pathogenicity and immune response are studied in animal models. Here, we present an important model system that enables studying neuropathogenicity of herpesviruses in the natural host. Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus that causes a devastating neurological disease (EHV-1 myeloencephalopathy; EHM) in horses. Like other alphaherpesviruses, our understanding of virus neuropathogenicity in the natural host beyond the essential role of viraemia is limited. In particular, information on the role of different viral proteins for virus transfer to the spinal cord endothelium in vivo is lacking. In this study, the contribution of two viral proteins, DNA polymerase (ORF30) and glycoprotein D (gD), to the pathogenicity of EHM was addressed. Furthermore, different cellular immune markers, including alpha-interferon (IFN-α), gamma-interferon (IFN-γ), interleukin-10 (IL-10) and interleukin-1 beta (IL-1β), were identified to play a role during the course of the disease.

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