Pathogenesis of equine herpesvirus-1 recombinants in a murine model

Among the infectious agents that plague the equine industry, Equine Herpesvirus-1 (EHV-1) is perhaps the best characterized. While horses usually recover from the initial respiratory infection without experiencing further problems, some horses develop sequelae, including abortion and neurological disease. Because of the potentially devastating outcomes of EHV-1 infections in a susceptible population, much work has focused on understanding the pathogenic mechanisms whereby EHV-1 causes disease, and how best to utilize this information to develop a more effective vaccine strategy. The establishment of a murine model of EHV-1 infection has provided researchers with an invaluable system in which to study virus-host interactions. Taking advantage of this animal model, our laboratory has undertaken studies to discern the underlying factors that contribute to EHV-1 pathogenesis and how the host responds to EHV-1 infection. Data acquired from numerous studies have shown that EHV-1 pathogenesis is multifactorial and involves a complex interplay between host and viral factors. Findings from studies in our laboratory indicate that glycoprotein I (gl) and glycoprotein E (gE) are EHV-1 virulence factors that contribute to the disease pathology observed in the lungs and brains of mice. The most striking differences in the outcomes of EHV-1 infections were observed after infection of mice with an attenuated EHV-1 KyA strain that lacks gl and gE and a KyA recombinant that has gl and gE restored (Kgl/gE/75). The lung pathology observed after infection with Kgl/gE/75 was associated with an inflammatory response that consisted of an increase in local chemokine production, resulting in an influx of inflammatory cells into the infected tissue. Clinical signs included loss of body weight, ruffled fur, inactivity, and, at later stages post-infection, neurological sequelae. The brain pathology was consistent with a meningoencephalitis, and consisted of lymphocytic cuffing of small blood vessels. This pathology is similar to that observed in infected horses experiencing neurological sequelae, and it is the first report of an EHV-1 isolate that is capable of causing pathology in the brains of mice. Overall, these data show that gl and gE contribute to EHV-1 pathogenesis in a murine model.