Equine herpesviruse types 1 and 4 both cause febrile rhinopneumonitis, it is EHV-1 that causes abortion, paresis and neonatal foal death. Referred The central lesion of these three conditions is an infection of cells lining the blood vessels (endothelial cells), leading to cell death within vessels, blood clot formation, and death to tissues serviced by these blood vessels. Recent research into vaccine development shows promise with a live temperature sensitive EHV-1 vaccine. Equine species (horse and donkeys) can be infected by 8 different types of herpesviruses EHV-1 and EHV-4 are the most clinically relevant pathogens. EHV-1 and EHV-4 where originally thought to be two subtypes of the same virus, EHV1, until recently viral genomic fingerprinting has made an official distinction btw the two. EHV-1 is a linear double stranded DNA genome with a potential to code for 77 different proteins. Endemic in horse populations around the world EHV-1 infection of suckling foals can occur as early as 30 days of age, thus lactating mares may be a primary source of EHV-1 infection of foals. The foals can then transmit the virus to other mares and foals. Stress can cause latent virus (resting virus…) to be reactivated. EHV-1 infection most likely starts early in life. EHV-1 strains are group according to the type of disease they cause. EHV-1 subtype 2 causes respiratory disease, while subtype 1 causes abortion. Respiratory disease acute, fever, anorexia, nasal discharge, ocular discharge, similar symptoms to EHV-4, however, EHV-1 causes much more severe disease Rhinopneumonitis develops due to bacterial colonization of the nasal passages EHV-1 replicates in the upper respiratory tract epithelial cells and local lymph nodes, and virus enters the bloodstream by attaching to leukocytes As horses age, the disease symptoms become less severe as they are repeatedly exposed and infected by the virus The leukocyte associated viraemia allows for virus to spread to endothelial cells lining blood vessels in the CNS and pregnant uterus, leading to CNS signs and abortion. Infection of endometrial blood vessels leads to inflammation of the blood vessels (vasculitis) and blood clot formation (thrombosis), leading to abortion of the fetus. The virus may actually cross the uteroplacental barrier and cause abortion in that way, or the birth of a live but infected foal which dies a few days afterward (neonatal foal death) Some strains of EHV-1 are immunosuppressive, causeing a leucopenia (decreased WBC count in circulating blood) Strains vary in their ability to cause abortion trimester 95 % of abortions occur int eh last 3rd of pregnancy. Why mares show an increased susceptibility to viral infection during late gestation has not been explained. Some host factors may actually be responsible for activating latently infected leukocytes, including equine chronic gonadotrophin (ECG) which is a hormone released from the placenta during gestation. Latency – is an important feature of EHV-1 infections, allowing the virus to survive and spread within the equine population. The virus can reside in tissues of the CNS or lymph system without causing any symptoms of disease, until the host is immunosuppressed and the virus becomes reactivated. Amongst The virus is isolated mostly from leukocytes and sometimes from nasal mucus Virus is shed in nasal mucus which plays a key role in the spread of EHV-1 infections. Spontaneous shedding of virus by occur after stressful events such as weaning, castration, relocation, terminal illness. Reactivation of latent EHV-1 may be asymptomatic but there may be significant shedding in nasal mucus. It is unknown whether or not reactivation of latent EHV-1 in pregnant mares results in abortion, but it is suspected to occur Latently infected leukocytes Infected aborted fetus another potential route of transmission – imp during abortion epidemics ******Immunoprophylaxis – fetuses EHV-1 infection of leukocytes is latent (latent in neural cells) Virus can be reactivated a long time after the primary infection Reduction in virus shedding in nasal mucus, local immunity may play a role (after challenge) Assess cellular immunity in horse and define protective immune mechanisms in EHV-1 infection is required to develop an effective vaccine that elicits the same responses Suggested that attenuated live EHV-1 vaccines are less likely to elicit the proper protective immune reactions (activate cytotoxic T lymphocytes) thus giving incomplete protection from the virus. Cytotoxic T lymphocytes are an essential part of the immune defense against many viral infections CTL cell frequency correlated with protection from EHV-1 abortion VACCINES – Control of respiratory disease due to EHV-1 Currently there are at least 12 multivalent EHV-1 and EHV-4 and 2 EHV-1 only multidose inactivated and two multi- dose live EHV-1 (one monovalent and one multivalent) vaccines marketed (Table 1). All 16 commercially available vaccines are for parenteral application only. However, most of these vaccines only claim protection against respiratory diseases due to EHV-1 and EHV-4. Currently in the EU only one product is licensed: an inactivated EHV-1 plus EHV-4 vaccine containing a carbomer as an adjuvant that claims protection against EHV-1 mediated abortions if administered during pregnancy at fifth, seventh and ninth months of gestation (Heldens et al., 2001). Nonetheless, much effort has also gone into developing live deletion mutant vaccines, mostly using EHV-1 strains, largely spurred on by the success achieved for other alphaherpesviruses, notably bovine herpesvirus 1 (BHV-1, Kaashoek et al., 1994) and pseudorabiesvirus New research into a live vaccine EHV-1 deletion mutant (some DNA is deleted from the virus) shows promise. Protected pregnant mares for up to 6 months after a single intranasal inoculation against febrile respiratory disease, virus shedding in nasal mucus and abortions due to EHV-1, also cross protected adult horses against EHV-4. Able to afford clinical protection against EHV-1 in suckling foals with maternally derived neutralizing antibody to EHV-1 and EHV-4 Multidose inactivated vaccines unlikely to be effective in protecting suckling foals Suckling foals are considered to be an important reservoir in the transmission of EHV-1 Target fro Immunoprophylaxis is suckling foals with maternal antibodies to eventually eliminate or reduce EHV-1. Pathogenesis: necrotizing vasculitis and thrombosis following lytic infection of endothelial cells lining capillaries in central nervous system, pregnant uterus EHV-4 causes similar vascular lesions, little role in abortion and paresis What host factors responsible for activating latent EHV-1 infected leukocytes and what conditions Suckling horse important role in virus transmission – target for control for EHV-1 Infection occurs early in life, need immunoprophylaxis to control infection of horses – not possible presently