Study: Single EHV-1 Mutation Can Cause Lethal Neurologic Disease

A single mutation in the genome of equine herpesvirus-1 (EHV-1) was "necessary and sufficient" to cause neurologic disease in horses in a new study, reported Cornell University researchers.

All strains of EHV-1 can cause respiratory disease and abortion, but only a subset of EHV-1 strains can cause neurologic disease said Nikolaus Osterrieder, DVM, DVM Habilitation (equivalent to PhD), and colleagues. It has previously been suggested that some strains of EHV-1 have a single genetic mutation in the gene that encodes the enzyme called DNA polymerase. This genetic mutation results in the enzyme sporting the amino acid aspartic acid at position 752 of the enzyme instead of an asparagine amino acid residue.

In light of this single, seemingly relatively innocuous substitution, the researchers wanted to determine whether the mutation was "not only necessary but also sufficient" to cause neurologic disease.

They studied this by taking a nonneurovirulent strain of EHV-1 obtained from an aborted equine fetus and inserting the single point mutation into its genome. Six horses were inoculated with the mutated virus and three horses were inoculated with the native, nonneurovirulent virus.

The nonneurologic form of EHV-1 resulted in only very mild upper respiratory disease--a complete absence of neurologic symptoms was reported. In contrast, two of the six horses inoculated with the mutated virus rapidly developed neurologic signs leading researchers to surmise that the single mutation was indeed responsible for the ability of the virus to cause neurologic disease in horses.

What continues to perplex the researchers is how a single mutation that is not in the enzyme's catalytic (active) site can have such a drastic impact. Research is ongoing.

The study, "A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease," was published in the July 2009 edition of the Journal of Infectious Diseases. The abstract is available on PubMed.

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