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.Equid herpesvirus 1 (EHV-1), a member of the subfamily Alphaherpesvirinae, is a highly prevalent equine pathogen that can cause a range of clinical signs, from respiratory distress to the induction of abortion, neonatal foal death, and occasionally neurological damage resulting in paralysis (9,14,19,33,37,61). The severity of disease resulting from EHV-1 infection is likely to be influenced by a number of factors, including the age and physical condition of the host; whether the infection is primary, a reinfection, or a reactivation of latent virus; the immune status of the host; and the pathogenic potential of the strain involved. In order to assess the relative importance of EHV-1 strain variation regarding disease outcome, it is necessary to develop methods enabling precise discrimination between genetic subgroups of interrelated strains. Previous studies have utilized DNA restriction fragment length polymorphism (RFLP) to separate field isolates of EHV-1 into subgroups according to characteristic restriction enzyme site changes and the presence of variable numbers of copies of short sequence repeats. These studies demonstrated a relatively low frequency of genetic polymorphism for EHV-1 and suggested that distinct strains of EHV-1 do exist in the field (3,4,8,25,32,41,54,57). However, the relative lack of variation of EHV-1 sequences between strains has resulted in too few RFLP variants to be identified for detailed epidemiological studies. Furthermore, although such analyses may be used for tracing the genetic relatedness of strains, they allow identification only of those genetic changes resul...

Infection with equid herpesvirus type 1 (EHV-1) leads to respiratory disease, abortion, and neurologic disorders in horses. Molecular epidemiology studies have demonstrated that a single nucleotide polymorphism resulting in an amino acid variation of the EHV-1 DNA polymerase (N752/D752) is significantly associated with the neuropathogenic potential of naturally occurring strains. To test the hypothesis that this single amino acid exchange by itself influences neuropathogenicity, we generated recombinant viruses with differing polymerase sequences. Here we show that the N752 mutant virus caused no neurologic signs in the natural host, while the D752 virus was able to cause inflammation of the central nervous system and ataxia. Neurologic disease induced by the D752 virus was concomitant with significantly increased levels of viremia (p = 0.01), but the magnitude of virus shedding from the nasal mucosa was similar between the N752 and D752 viruses. Both viruses replicated with similar kinetics in fibroblasts and epithelial cells, but exhibited differences in leukocyte tropism. Last, we observed a significant increase (p < 0.001) in sensitivity of the N752 mutant to aphidicolin, a drug targeting the viral polymerase. Our results demonstrate that a single amino acid variation in a herpesvirus enzyme can influence neuropathogenic potential without having a major effect on virus shedding from infected animals, which is important for horizontal spread in a population. This observation is very interesting from an evolutionary standpoint and is consistent with data indicating that the N752 DNA pol genotype is predominant in the EHV-1 population, suggesting that decreased viral pathogenicity in the natural host might not be at the expense of less efficient inter-individual transmission.

Equine herpesvirus 1 (EHV-1) is an important equine pathogen that causes respiratory disease, abortion, neonatal death and paralysis. Although vaccines are available, they are not fully protective and outbreaks of disease may occur in vaccinated herds. Therefore, there is an urgent need for effective antiviral treatment. For three abortigenic (94P247, 97P70 and 99P96) and three neuropathogenic isolates (97P82, 99P136 and 03P37), the effect of acyclovir, ganciclovir, cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) and foscarnet on plaque number was studied. Additionally, for isolate 97P70, the effect on plaque size was investigated. Ganciclovir was most potent in reducing plaque number, followed by PMEDAP and acyclovir. Adefovir and cidofovir were less effective and foscarnet was the least effective compound. There were no differences detected for acyclovir, ganciclovir, adefovir and PMEDAP between the abortigenic and neuropathogenic isolates. One abortigenic isolate (99P96) was more susceptible to cidofovir and two neuropathogenic isolates (99P136 and 03P37) were less susceptible to foscarnet. For isolate 97P70, all compounds resulted in a significant reduction of plaque size. The most remarkable effect was observed for cidofovir. It was 40-fold more effective in reducing plaque size than in reducing plaque number. In conclusion, ganciclovir was the most potent compound and therefore, may be a valuable candidate for the treatment of EHV-1 infections in horses. The antiviral effect of foscarnet on plaque number was highly dependent on the viral isolate tested. Therefore, it is no valuable antiviral for the treatment of herpesvirus-infections. Cidofovir, although less effective in reducing plaque number, had a strong effect on plaque size. #

Equine Herpes virus-1 (EHV-1) is one of the most common respiratory pathogens of the horse. EHV-1 induces several clinical signs of disease ranging in severity, from mild respiratory distress to abortion in pregnant mares, neonatal foal death and neuropathogenic disorders. This review details some aspects of EHV-1 biology, its life cycle and pathogenicity in the natural host. Protective immunity stimulated by natural EHV-1 infection, which is short lived and depends of both humoral and cellular immune responses, will also be treated here. Vaccination remains today one of the best options to fight EHV-1 infection and several different strategies of vaccination that have been investigated and developed over the past decades will be presented in this report. EHV-1 Eq. abortion virus α2 Respiratory, abortion, neurological EHV-2 Eq. cytomegalovirus γ3 NA EHV-3 Eq. coital exanthema virus α Coital exanthema EHV-4 Eq. rhinopneumonitis virus α2 Respiratory Equus caballus EHV-5 Eq. cytomegalovirus γ3 NA AHV-1/EHV-6 Related to EHV-3 α Coital exanthema AHV-2/EHV-7 Related to EHV-2 γ3 NA Equus asinus AHV-3/EHV-8 Related to EHV-1 α Rhinitis Gazella thomsoni GHV-1/EHV-9 Similar to EHV-1/EHV-8 α Ga.&Eq. neurological Eq. = equine; Ga. = gazelle; NA= not associated.

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