Interferon Response Inhibition by Equine Herpesvirus-1

Equine herpesvirus-1 (EHV-1) is a one of the leading causes of respiratory disease in horses. It is an especially worrisome disease because it can produce symptoms including neurological signs known as equine herpesviral myeloencephalopathy (EHM) that could lead to the death of the affected horse. There are vaccines for EHV-1 but control of the disease has been very difficult because, like most herpesviruses, EHV-1 appears to have many ways of avoiding host immune responses. From our previous Grayson-Jockey Club Research Foundation-supported project, we have evidence that in cell culture, one of the ways EHV-1 avoids immune responses is by blocking the Type-I interferon (IFN) response. The Type-I IFN response is important as a non-specific first line of defense against many virus infections, by making cells more resistant to virus infection. But what the virus actually does to interferon responses in the horse, as compared with cell culture, is not clear and the cell culture model may be misleading. To determine this we propose to study whether EHV-1 blocks the Type-I IFN response in tissues taken directly from the respiratory track of the horse. This brings in a new factor, that a different type of IFN called Type-III IFN may also be involved in protecting those respiratory tissues. So we will also study whether EHV-1 blocks Type-III IFN responses. With this knowledge we will have a stronger foundation for the development of treatments to strengthen the IFN-based innate immune responses against EHV-1 and improve the horse’s chances of speedy recovery from this disease. This will have a major impact on the health and welfare of horses that are exposed to EHV-1 at events, racetracks, or training stables where EHM neurological disease outbreaks can cause previously healthy horses to be euthanized. It might also further reduce the risk of abortions in pregnant mares that are exposed to EHV-1.