Equine herpesvirus myeloencephalopathy-related mutations in EHV-1 DNA polymerase allow EHV-1 to grow at elevated temperatures

Equine herpesvirus myeloencephalopathy (EHM) caused by equine herpesvirus type 1 (EHV-1) is a major threat to the equine industry because of its devastatating impact on animal welfare and performance. A specific single nucleotide polymorphism (SNP) (G2254/D752) in the EHV-1 ORF30 gene encoding DNA polymerase was previously shown to be a marker of the strain of EHV-1 that causes EHM. However, the effect of this SNP has never been resolved. Clinical findings indicated that fever and higher viremia levels are associated with the onset of EHM. No studies have examined EHV-1 growth at elevated temperatures so far. We found that EHV-1 with the D752 SNP replicated at elevated temperatures, and EHV-1 without it did not. We also found that EHV-1s isolated from horses with EHM could grow at elevated temperatures and most non-EHM isolates were suppressed by elevated temperatures. EHV-1s that can replicate at elevated temperatures have this SNP or one other SNP in ORF30. This appears to be the first report to show an association between EHM and the ability of EHV-1 to grow at elevated temperatures. (177 words) ImportanceEquine herpesvirus myeloencephalopathy (EHM) caused by equine herpesvirus type 1 (EHV-1) is a major threat to the equine industry because of its impact on animal welfare and performance. A specific single nucleotide polymorphism (SNP) (G2254/D752) in EHV-1 ORF30 gene encoding DNA polymerase (UL30) was previously shown to be a marker of EHM. However, the effect of this SNP has never been resolved. Here we show that this and one other SNP in UL30 are associated with replication capacity at elevated temperatures. (81 words)