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Equine herpesvirus and the major histocompatibility complex (MHC)

The goal of this project is to determine the importance of MHC class I molecules as cell-surface receptors for entry of equine herpes virus type 1 (EHV-1) and type 4 (EHV-4).  EHV-1, one of the major uncontrolled pathogens of the horse worldwide, can cause abortions and severe neurologic disease, two syndromes that usually follow respiratory disease, and can affect large numbers of horses.  EHV-1 manifests itself systemically, while EHV-4 remains restricted to the upper respiratory tract. EHV-1-induced myeloencephalopathy is often fatal.  Farms, stables and hospitals with active EHV-1 infections are quarantined, causing disruption of normal activity and economic losses.  Large outbreaks of EHV-1 infections in the US and Canada in 2011 have reinforced the need for better control measures.

Two recent studies have identified equine MHC class I molecules as receptors for EHV-1, while the EHV-4 receptor remains elusive.  The precise mechanisms of EHV-1 and EHV-4 entry and potential co-receptor molecules are not known. EHV-1 can utilize endosomal (low pH) entry in lymphocytes but can directly fuse with the plasma membrane of epithelial and endothelial cells at neutral pH.  The role of MHC class I molecules in the different entry pathways remains unknown.  We hypothesize that MHC class I molecules serve as a major entry pathway for EHV-1 and EHV-4 in certain cell types and that different MHC class I molecules will have receptor functions of varying efficiency, thus determining host susceptibility to infection.