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The equine herpesviruses type 1 (EHV-1) and 4 (EHV-4) are ubiquitous pathogens that affect horse populations on all continents. Despite widespread vaccination, EHV-1 and EHV-4 infections remain a permanent risk. While the two viruses share a high degree of genetic and antigenic similarity, they differ significantly in host range and pathogenicity. Compared to EHV-4, which mainly infects horses and causes respiratory disease, EHV-1 has a broader host range and can result in respiratory disease, abortions, neonatal death, and equine herpesvirusmyeloencephalopathy (EHM). Recent studies have elucidated a number of mechanisms that may, at least partly, explain the differential pathogenic potential of the two viruses. While both EHV-1 and EHV-4 can escape host immune responses and establish latent infection, there are differences with respect to virus entry and their ability to interfere with the innate immune response. Understanding the virus' repertoire of immunomodulatory mechanisms may lead the way to develop more efficient vaccines.