Equine Viral Arteritis Udeni B.R. Balasuriya,

BVSc, MS, PhD

KEYWORDS  Equine viral arteritis  Equine arteritis virus  EAV  EVA KEY POINTS  Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA).  EVA is a respiratory and reproductive disease of the horse that occurs throughout the world.  Most EAV infections are inapparent (or subclinical); however, acutely infected animals may develop a wide range of clinical signs.  Virus causes abortion in pregnant mares and a high proportion of acutely infected stallions become persistently infected and shed the virus in semen.  EAV infection can cause a severe fulminating interstitial pneumonia and a progressive pneumoenteric syndrome in young foals.

VIRUS

EAV was first isolated from the lung of an aborted fetus after an extensive outbreak of respiratory disease and abortion on a Standardbred breeding farm near Bucyrus, Ohio, in 1953.1,2 After isolation of the causative virus (EAV) and description of characteristic vascular lesions, EVA was identified as an etiologically distinct disease of the horse.1 EAV is a small enveloped, positive-sense, single-stranded RNA virus that is the prototype virus in the family Arteriviridae (genus Arterivirus), order Nidovirales, a taxonomic grouping that includes porcine reproductive and respiratory syndrome virus, simian hemorrhagic fever virus, lactate dehydrogenase-elevating virus of mice, and recently identified wobbly possum disease virus of free-ranging Australian brushtail possums (Trichosurus vulpecula) in New Zealand.3,4 The molecular properties of EAV were reviewed by Balasuriya and colleagues5,6 (2013 and 2014). Briefly, the EAV genome length varies between 12,704 and 12,731 base pair among different viral strains and includes a 50 leader sequence (224 nucleotides) and at least 10 open reading frames (ORFs).5 The 2 most 50 -proximal ORFs (1a and 1b) occupy approximately three-fourths of the genome and encode

This work was partially supported by Agriculture and Food Research Initiative competitive grant no. 2013-68004-20360 from the USDA National Institute of Food and Agriculture. Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40546-0099, USA E-mail address: [email protected] Vet Clin Equine 30 (2014) 543–560 http://dx.doi.org/10.1016/j.cveq.2014.08.011 vetequine.theclinics.com 0749-0739/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.

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2 replicase polyproteins (pp1a and pp1ab). These precursor proteins are extensively processed after translation into at least 13 nonstructural proteins (nsp1–12, including nsp7 a/b) by 3 viral proteases (nsp1, 2, and 4).5 The structural proteins of EAV include seven envelope proteins (E, GP2, GP3, GP4, ORF5a protein, GP5, and M [encoded by ORFs 2a, 2b, 3-4, 5a, 5b, and 6]) and a nucleocapsid protein (N [encoded by ORF7]). All the structural protein encoding ORFs are located at the 3 proximal quarter of the genome (Fig. 1).5,7 Three of the minor envelope glycoproteins (GP2, GP3, and GP4) form a heterotrimer in the EAV particle, and the M (nonglycosylated) and GP5 (glycosylated) proteins form a disulfide-linked heterodimer.5,7 Organ samples and tissue culture fluid containing EAV can be stored frozen (70 C to 80 C) for decades without significant loss of virus infectivity. The virus also survives in cryopreserved semen samples and embryos for many years. EAV remain infectious 75 days at 4 C, between 2 to 3 days at 37 C, and 20 to 30 minutes at 56 C. EAV is readily inactivated by lipid solvents (ether and chloroform) and by common disinfectants and detergents. CLINICAL SIGNS

The clinical signs displayed by EAV-infected horses depend on a variety of factors, including the genetics, age, and physical condition of the horses; challenge dose; route of infection; strain of virus; and environmental conditions.8–11 Although there is only 1 known serotype of EAV, there is significant variation in virulence phenotype between EAV field strains.5,11 Based on the clinical severity of the disease during natural outbreaks, EAV field strains could be segregated into viruses that cause moderate to severe disease (eg, EAV KY84, EAV AZ87, EAV IL93, and EAV PA96), mild disease (eg, EAV SWZ 64, EAV AUT68, EAV IL94, and EAV CA97) and asymptomatic infection (EAV KY63, EAV PA76, EAV KY77, and EAV CA95; Moore and colleagues,12 2002). Similarly, laboratory and vaccine strains differ significantly in their virulence phenotype from the highly virulent, horse-adapted Bucyrus strain (virulent Bucyrus

Fig. 1. Virion architecture. EAV particle consists of a nucleocapsid (N) and 7 envelope proteins, which include 2 major envelope proteins (GP5 and M form a dimer), 3 minor envelope glycoproteins (GP2, GP3, and GP4 form a trimer), and 2 other minor envelope proteins (E and ORF5a protein).

Equine Viral Arteritis

High neutralizing antibody titers in persistently infected stallions

Virus Titer PFU/mL

Viremia (3-19 DPI)

Long-term shedder

105

1:1024 1:256

104 Neutralizing antibody response following acute infection

103 102 101

Short-term shedder

1:4 2 yr Time

Persistently infected carrier stallions – high neutralizing antibody titers and no viremia. Virus titers in semen.

Fig. 2. Outcome of EAV infection.

1:16

Intermediate shedder

1 mo 2 mo 6 mo 7 mo

1:64

3 yr

Neutralizing Antibody Titer

strain [VBS] of EAV; ATCC VR-796) of EAV, and the highly attenuated modified live virus (MLV) vaccine derived from it, to the highly attenuated recombinant EAV 030 strain derived from an infectious cDNA clone of the virus.6 With the sole and notable exception of the experimentally derived and highly horse-adapted EAV VBS, other strains and field isolates of EAV very rarely cause fatal infection in adult horses.11,13 Most EAV infections are inapparent, especially those that occur in mares bred to persistently infected stallions.8,14,15 The incubation period of 2 to 14 days (usually 6 to 8 days following venereal exposure) is followed by fever of up to 41 C that may persist for 2 to 9 days (Fig. 2).5,6 Very young, old, debilitated, and immunosuppressed horses are predisposed to severe EVA and may develop a wide range of clinical signs, including fever, depression, anorexia, dependent edema (scrotum, ventral trunk, and limbs), stiffness of gait, conjunctivitis, lacrimation, periorbital and supraorbital edema, respiratory distress, urticaria (that may be localized to sides of the neck or face or may be generalized over most of the body), and leukopenia.5,8 The most consistent clinical features of EAV infection are pyrexia and leukopenia.16–18 Less frequently observed signs include icterus; photophobia; corneal opacity; coughing and dyspnea; abdominal pain and diarrhea; ataxia; petechiation of the nasal mucosa, conjunctiva, and oral mucous membranes; submaxillary and submandibular lymphadenopathy; and adventitious edema in the intermandibular space, beneath the sternum, or in the shoulder region.1,2,19–25 The virus causes abortion in pregnant mares. Abortion rates during natural outbreaks of EVA can vary from less than 10% to 71% of infected mares.8,22 EAVinduced abortions can occur at any time between 3 and 10 months of gestation. The abortigenic potential of different strains of EAV has not been adequately compared but it seems that strains differ in their abortigenic potential as they do in their virulence characteristics. EAV infection can cause a severe fulminating interstitial pneumonia in neonatal foals and a progressive pneumoenteric syndrome in older foals.9 A high proportion of acutely infected stallions (10%–70%) become persistently infected and shed the virus in semen; however, there is no evidence of any analogous persistent infection in mares, geldings, or foals (Fig. 3).8,15,26 With the exception of persistently infected stallions, EAV is cleared from the tissues of infected horses by 28 days after the exposure. The virus persists in the ampulla and the accessory sex glands of the male reproductive tract and the establishment and maintenance of the

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Fig. 3. Transmission of EAV between horses and the central role of carrier stallion in maintenance and perpetuation of the virus in equine populations.

Equine Viral Arteritis

carrier state in stallions is testosterone-dependent.8 Stallions may undergo a period of temporary subfertility associated with decreased libido, sperm motility, and concentration, and an increased percentage of morphologically abnormal sperm in ejaculates during acute EAV infection. These changes can persist for up to 6 to 7 weeks after experimental EAV infection of stallions.8,27 During acute infection, scrotal edema and fever could exert independent effects on all the semen quality parameters, including total motile (TMOT) and progressively motile (PMOT) sperm cells, total number of spermatozoa ( TNS), curvilinear velocity ( VCL), percentage of live spermatozoa ( LS), and percentage of morphologically normal spermatozoa (MNS). It has been shown that following experimental infection, there is significant decrease in all parameters evaluated for semen quality (TMOT and PMOT, TNS, LS, MNS, VCL) between 9 to 76 days postinfection (DPI).28 The common sperm abnormalities include detached heads, head and proximal droplet defects, and tail, midpiece, and acrosome defects. Semen quality is apparently normal in persistently infected stallions, despite high titer virus shedding in the semen. Because virus titers remained high long after semen quality returned to baseline, the virus seems to exert little to no direct effect (see Fig. 2).28 Venereal infection of mares by persistently infected carrier stallions does not seem to result in subsequent fertility problems.8 EPIDEMIOLOGY

EAV is distributed throughout the world, although the seroprevalence of EAV infection varies between countries and horses of different breeds and age in the same country. Serologic surveys have shown that EAV infection has occurred among horses in North and South America, Europe, Australia, Africa, and Asia.8,29 Other countries, such as Iceland and Japan, are apparently free of the virus. Recent studies have shown that New Zealand is also free of EAV.30 In the United States, a very high percentage of adult Standardbred and Saddlebred horses are seropositive (70%–90% and 8%–25%, respectively) for EAV, compared with the Thoroughbred population where seroprevalence is very low (

Equine viral arteritis.

Equine arteritis virus (EAV), the causative agent of equine viral arteritis (EVA), is a respiratory and reproductive disease that occurs throughout th...
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