Epidemiology, disease and control of infections in ruminants by herpesviruses--an overview.

There are at least 16 recognised herpesviruses that naturally infect cattle, sheep, goats and various species of deer and antelopes. Six of the viruses are recognised as distinct alphaherpesviruses and 9 as gammaherpesviruses. Buffalo herpesvirus (BflHV) and ovine herpesvirus-1 (OvHV-1) remain officially unclassified. The prevalence of ruminant herpesviruses varies from worldwide to geographically restricted in distribution. Viruses in both subfamilies Alphaherpesvirinae and Gammaherpesvirinae cause mild to moderate and severe disease in respective natural or secondary ruminant hosts. Accordingly, the economic and ecological impact of the viruses is also variable. The molecular characteristics of some members have been investigated in detail. This has led to the identification of virulence-associated genes and construction of deletion mutants and recombinant viruses. Some of the latter have been developed as commercial vaccines. This paper aims to give an overview of the epidemiology and pathogenesis of infection by these viruses, immuno-prophylaxis and mechanisms of recovery from infection. Since there are 128 ruminant species in the family Bovidae, it is likely that some herpesviruses remain undiscovered. We conclude that currently known ruminant alphaherpesviruses occur only in their natural hosts and do not cross stably into other ruminant species. By contrast, gammaherpesviruses have a much broader host range as evidenced by the fact that antibodies reactive to alcelaphine herpesvirus type 1 have been detected in 4 subfamilies in the family Bovidae, namely Alcelaphinae, Hippotraginae, Ovibovinae and Caprinae. New gammaherpesviruses within these subfamilies are likely to be discovered in the future.

Variation in immunogenicity of ruminant pestiviruses as determined by the neutralisation assay.

Immunogenicity in naive three-month-old Friesian bull calves of nine ruminant pestiviruses, three each of type 1 bovine virus diarrhoea virus (BVDV), type 2 BVDV and border disease virus (BDV) was directly compared in reciprocal cross-neutralisation tests using sera obtained eight weeks after intranasal and intravenous inoculation with live virus. Cytopathic (CP) type 1 BVDV strain C86, non-cytopathic (NCP) type 2 BVDV strain 890 and NCP BDV strain V2536/2 were found to elicit significantly broad cross-neutralising antibodies against viruses in other species whereas other virus strains in all three species produced a much more pronounced homologous and/or species specific response. Results are clearly relevant in the selection of strains for vaccines against diseases caused by these successful, economically important ubiquitous viruses.

Efficacy of a live equine herpesvirus-1 (EHV-1) strain C147 vaccine in foals with maternally-derived antibody: protection against EHV-1 infection.

REASONS FOR PERFORMING STUDY: Currently, there is no recommended immunoprophylaxis against febrile respiratory diseases due to equine herpesvirus-1 (EHV-1) and -4 (EHV-4) in horses below age 5-6 months. This is because of interference by maternally-derived antibody (MDA) of vaccines. OBJECTIVE: Unweaned equine foals are an important reservoir of EHV-1 transmission; therefore, we experimentally assessed the efficacy of a live EHV-1 vaccine in foals age 1.4-3.5 months with MDA. METHODS: Following vaccination and challenge, parameters assessed were virus shedding in nasal mucus, leucocyte-associated viraemia, circulating virus neutralising antibody activity and clinical reactions. RESULTS: Controlled challenge showed that a single intranasal dose of the vaccine afforded partial but significant protection against febrile respiratory disease, virus shedding and viraemia due to EHV-1 infection, despite virus-neutralising MDA. CONCLUSIONS AND POTENTIAL RELEVANCE: The prospective vaccine would be a significant step forward in reducing the incidence of the disease caused by EHV-1 infection.

Derivation and characterisation of a live equid herpes virus-1 (EHV-1) vaccine to protect against abortion and respiratory disease due to EHV-1.

A German abortion isolate of EHV-1 (strain M8) was grown in equine dermal (ED) cells at a low multiplicity of infection in presence of 5-bromo-2-deoxy uridine. The resulting stock was dialysed, titrated and cloned by terminal dilution in ED cells grown in 96-well microtitration plates. Of 192 clones each originating from a single focus, clone 147 (C147) was found to be restricted for growth at and above temperatures of 38.5 degrees C. It was also restricted for growth at 37 degrees C in rabbit kidney (RK-13) cells which are widely used for the isolation and titration of EHV-1; hence clone 147 was EHV-4-like. Clone 147 showed a remarkable efficacy as a vaccine in protecting conventional pregnant Welsh Mountain pony mares against abortions due to EHV-1. A single intranasal (IN) vaccination protected five out of six (83.3%), and four out of five (80%) of mares upon challenge 4 and 5-6 months, respectively, after the immunisation, whereas all six unvaccinated mares aborted between 9 and 19 days after IN EHV-1 challenge. With the exception of the day 9 abortion, foetuses of the remaining five mares were EHV-1 infected. Placenta from the early aborting mare was, however, EHV-1 positive. Both groups of vaccinated mares were also significantly protected against clinical reaction (notably pyrexia), nasal shedding and viraemia following challenge infection.

Equid herpesvirus (EHV-1) live vaccine strain C147: efficacy against respiratory diseases following EHV types 1 and 4 challenges.

The temperature sensitive and host range mutant clone 147 of equine herpesvirus 1 (EHV-1) was assessed for its ability to protect conventional, susceptible adult horses against respiratory infection by EHV-1 and equine herpesvirus 4 (EHV-4). Intranasal (IN) vaccination with 5.2 log(10) TCID(50) did not cause adverse clinical reactions although a limited virus shedding and viraemia (leukocytes) was observed in 11 of 15 and 10 of 15 vaccinated horses respectively. All 15 vaccinated horses showed a significant seroresponse to both EHV-1 and EHV-4 for virus neutralising (VN) antibody. None of 14 control horses shed virus or became viraemic or seroconverted prior to challenge. EHV-1 challenge (dose 6.0 log(10)) 6 weeks after vaccination resulted in pyrexia in all eight control horses while eight vaccinated horses remained unaffected. Six control horses developed nasal discharge, five of which were mucopurulent nasal discharge (mean duration 3.2 days) which also occurred in four vaccinated horses for 1 day. All eight control horses shed challenge EHV-1 at a significantly higher level (group mean titre 2.6+/-0.4 log(10) TCID(50) per sample) and for much longer (mean duration 4.8+/-1.5 days) than that (group mean titre 1.4+/-0.8 log(10) TCID(50) per sample and mean duration 1.5+/-0.5 days) in six vaccinated horses. Furthermore, all eight control horses became viraemic (mean duration 2.9 days) but viraemia did not occur in eight vaccinated horses. Following EHV-1 challenge, all eight control horses showed a significant VN antibody rise to both EHV-1 and EHV-4 but this occurred in only one vaccinated horse and to EHV-4 only. In EHV-4 challenge (dose of 4.2 log(10) TCID(50)) of a separate pair of seven vaccinated and six control horses, 6 weeks after EHV-1 vaccination resulted in pyrexia (mean duration 2.3 days) and nasal discharge (mean duration 1.8 days) in three and five control horses respectively but the only reaction observed in the vaccinated group was nasal discharge for 1 day in one animal. All six control animals shed virus (mean titre 2.5+/-0.6 log(10) TCID(50) per sample and mean duration 2+/-0.6 days) compared to one vaccinated animal. Although EHV-4 viraemia is rare, 3 of 6 control horses became viraemic after EHV-4 challenge but this was not observed in vaccinated horses. After EHV-4 challenge 3 and 5 of 6 control horses seroconverted for VN antibody to EHV-1 and EHV-4 respectively; a non-responsive control horse had high level of pre-existing VN antibody to EHV-4. However, only 1 of 7 vaccinated horses showed a significant antibody rise and only to EHV-4.