Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic disease outbreaks.

Equid herpesvirus 1 (EHV-1) can cause a wide spectrum of diseases ranging from inapparent respiratory infection to the induction of abortion and, in extreme cases, neurological disease resulting in paralysis and ultimately death. It has been suggested that distinct strains of EHV-1 that differ in pathogenic capacity circulate in the field. In order to investigate this hypothesis, it was necessary to identify genetic markers that allow subgroups of related strains to be identified. We have determined all of the genetic differences between a neuropathogenic strain (Ab4) and a nonneuropathogenic strain (V592) of EHV-1 and developed PCR/sequencing procedures enabling differentiation of EHV-1 strains circulating in the field. The results indicate the occurrence of several major genetic subgroups of EHV-1 among isolates recovered from outbreaks over the course of 30 years, consistent with the proposal that distinct strains of EHV-1 circulate in the field. Moreover, there is evidence that certain strain groups are geographically restricted, being recovered predominantly from outbreaks occurring in either North America or Europe. Significantly, variation of a single amino acid of the DNA polymerase is strongly associated with neurological versus nonneurological disease outbreaks. Strikingly, this variant amino acid occurs at a highly conserved position for herpesvirus DNA polymerases, suggesting an important functional role.

Comparison of hamster and pony challenge models for evaluation of effect of antigenic drift on cross protection afforded by equine influenza vaccines.

REASONS FOR PERFORMING STUDY: Vaccination and challenge studies in ponies are the most relevant experimental system for predicting whether strains included in equine influenza vaccines are relevant, but they are difficult to perform. OBJECTIVES: In order to investigate the feasibility of using a small animal model, results of a cross-protection study in hamsters were compared with those from a previous pony challenge experiment. METHODS: Animals were immunised with inactivated vaccines containing one of 4 strains of equine influenza A H3N8 subtype virus isolated over a 26 year period (1963 to 1989), then challenged with a 1989 strain. RESULTS: Although there was no significant difference in titres of excreted virus between groups of vaccinated ponies, hamsters immunised with heterologous strains had significantly higher virus titres in the lung than hamsters vaccinated with the homologous strain. In both ponies and hamsters, the number of animals excreting virus was greater the earlier the isolation date of the vaccine strain, although this was only significant in the hamster study. CONCLUSIONS: Despite differences, the overall conclusion of both the pony and hamster models was that heterologous vaccines may be less effective than homologous vaccines at preventing virus excretion. POTENTIAL RELEVANCE: Further validation is required, but the hamster model shows potential for preliminary assessment of the effects of antigenic drift on vaccine efficacy.