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Adenovirus infections

Preferred citation: Anipedia, www.anipedia.org: JAW Coetzer and P Oberem (Directors) In: Infectious Diseases of Livestock, JAW Coetzer, GR Thomson,
NJ Maclachlan and M-L Penrith (Editors). SK Tikoo, TA Woldemariam, VK Monoharan and S Kulanayake , Adenovirus infections, 2018.
Adenovirus infections

Adenovirus infections

Previous authors: G R THOMSON

Current authors:
S K TIKOO - Professor and Research Fellow, School of Public Health\VIDO-InterVac, Director, Vaccinology & Immunotherapeutics Program, University of Saskatchewan, Saskatoon, SK, Canada
T A WOLDEMARIAM - PhD Candidate, Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada
V K MANOHARAN - Post-doctoral Fellow, VIDO-INTERVAC, University of Saskatchewan, 120 Veterinary Road, Saskatchewan, Canada
S M P KULANAYAKE - PhD candidate, Vaccinology & Immunotherapeutics Program University of Saskatchewan, Saskatoon, SK, Canada

GENERAL INTRODUCTION: ADENOVIRIDAE

Introduction

Since the first isolation of adenovirus in humans by Enders et al (1956),45 adenoviruses have been isolated from mammals, birds, reptiles including turtles, and fish,  which are mainly involved in mild clinical infections. Among the major domestic livestock species, adenovirus infections have been diagnosed in cattle, sheep, goats, pigs and horses.

It is probable that all vertebrates have one or more adenoviruses with which they co-evolved so only a few cause disease in their natural hosts. Most adenoviruses are associated with the upper respiratory or digestive tracts of their hosts and, in some cases infection may be prolonged, apparently as part of a transmission strategy. Well-known exceptions in respect of pathogenicity in domestic animals are the viruses that cause infectious canine hepatitis and contribute to the kennel cough syndrome.

Apart from equine mastadenovirus 1 and 2 infection of Arabian foals suffering from severe combined immune deficiency, no clearly defined disease syndrome of livestock, other than poultry, has been shown unequivocally to be caused by an adenovirus. Adenoviruses are, however, common in children and people suffering from immune deficiencies, such as those resulting from chemotherapy following organ transplantation or due to human immunodeficiency virus infection.

Adenoviruses have been used for many decades to research fundamental phenomena in the field of virology, i.e. for academic research. That, among other things, led to the discovery that adenoviruses are able to cause tumours in newborn rodents. However, this does not occur in natural hosts. More recently there has been research into use of adenoviruses to construct recombinant viruses for use as vaccines against other viral infections, e.g. foot and mouth disease.

Adeno-associated viruses (AAVs) are parvoviruses classified in the genus Dependovirus, dependent on co-infection of cells with an adenovirus in order to be able to replicate. These viruses have been identified in humans, cattle, sheep, horses, dogs and birds. However, no AVV has so far been associated with disease.

For more information on the classification and general characteristic on adenoviruses the General Introduction: Adenoviridae should be consulted.

Adenovirus infections of cattle

Introduction

Adenovirus infections of cattle probably occur universally and most infections are subclinical. Since its first isolation from faecal samples of a cow in USA,63 bovine adenoviruses (BAdVs) have been isolated from healthy and sick calves suffering from diarrhoea and/or respiratory disease.128 Depending on the serotype of the virus, it can cause a variety of clinical signs, including pneumonia, diarrhoea, conjunctivitis and polyarthritis in young animals. Though BAdV infections have been associated with a variety of respiratory and alimentary tract diseases, their role in the causation of these diseases remains uncertain. At present, 11 known BAdV serotypes are classified into two genera, namely Mastadenovirus (BAdV-1,2,3,9 and 10) and Atadenovirus (BAdV-4,5,6,7,8 and strain Rus).75

Aetiology

For more information on the characteristics of adenoviruses the General Introduction: Adenoviridae should be consulted

The best characterized serotype is BAdV-3.3 The genome of BAdV-3 is divided into E, I and L regions. Structural proteins are encoded by E2 (terminal protein ), I (pIX, IVa2) and L (hexon, penton, fiber, IIIa, VI, VIII, IX, V, VII, Mu, TP,  protease) regions. The nonstructural proteins are encoded by E (E1, E3 and E4), E2 (DNA binding protein; RNA polymerase II) and L (52K, 100K, 33K, 22K) regions.3, 106

Although intitial attachment of BAdV-3 to host cells involves interaction of the knob region of penton fibres with sialic acid attached to 97 kDa and 34 kDa cellular proteins,79 the existence of secondary interaction of penton fibres with cellular receptors is not clear. Following internalization of virus capsid containing genome into endosomes, the infectious BAdV-3 are produced as described in the General Introduction: Adenoviridae.

Epidemiology

About  25 to 87 per cent of cattle sera are positive for BAdV  antibodies, indicating high prevalence rates of infection in different geographic locations and in various sex and age groups. It is therefore safe to presume that infections with adenoviruses are widespread in cattle populations.20, 22, 77, 117, 126 For example, 76 and 59 per cent of calf sera collected at two Austrian abattoirs had virus neutralizing antibodies against selected serotypes.20, 89 In a group of 29 heifers monitored serologically in Idaho, USA, from birth to 24 months of age, there were 28 BAdV- 3 and 33 BAdV- 7 infections, some of which occurred in the face of maternally-derived antibody.117 Asymptomatic cattle populations have been shown to commonly shed multiple viruses belonging to different BAdV serotypes,112 which supports existing serologic data showing the widespread, asymptomatic exposure of cattle to most BAdV serotypes.47, 50, 67 Interestingly, BAV-3 is a common pathogen of  dairy calf pneumonia in dairy herds in Mashhad area of Khorasan Razavi province, Iran.105

It is presumed that most infections occur by close and direct respiratory transmission or by the faecal–oral route. The virus has been detected for up to eight days in the respiratory secretions and rectal swabs of experimentally infected calves.92 Transplacental transmission has also been shown,7 but how common this is remains uncertain.

Apart from evidence of infection in sheep and African buffaloes (Syncerus caffer),  antibodies to BAdV-3 were detected in the sera of Arabian oryx (Oryx leucoryx) in UAE48 and llamas in Argentina.100 Antibodies to BAdV-3/-7 were detected in sera of pronghorn antelope (Antilocapra americana) in Idaho.118 However, it is not clear whether this was cross-reacting antibody or antibody specific to these two serotypes.

Pathogenesis, clinical signs and pathology

Although most adenovirus isolations have been made from cattle that are apparently healthy,39, 63, 64, 119 a variety of conditions, most of which involve the respiratory or alimentary tract, have been associated with adenovirus infections (Table 1).

The two most comprehensive studies on the association between adenoviruses and disease in cattle, both conducted in Britain, reached conflicting conclusions.

One, based on the isolation of viruses from nearly 1 600 diseased and healthy calves over a period of 43 months, found that adenoviruses played no significant part in the causation of respiratory illness.119 The other, based on serological monitoring of young bulls over a period of 18 months, demonstrated a statistically significant association between serological responses to adenovirus infections, especially those caused by subgroup 1 viruses, and the occurrence of clinical disease.22

Similarly, experimental infection of calves with a variety of BAdV serotypes2, 7, 91, 92 has resulted in either no obvious ill effect or a variety of non-lethal respiratory or enteric conditions. The lungs of experimentally infected calves that developed lesions had necrotizing and proliferative bronchiolitis, and sometimes bronchopneumonia, with intranuclear inclusions in bronchiolar epithelial cells.

Table 1 Some associations reported between adenovirus infections and health status in cattle

CLINICAL SYNDROME

TYPE AND AGE OF CATTLE

SEROTYPE

REFERENCE

None

Heifers: 0 to 24 months

BAdV-3,-7

117

Calves

Various

119

Cow

BAdV-2 (WBR1)

39

Cow

NS

63

Calf 
Calves

NS 
BAdV-7                  

47, 64

Keratoconjunctivitis

NS

Various

130, 131

Respiratory disease

Bull calves

Various (esp. subtype A)

22

Calves

BAdV-3

77

Feedlot cattle

BAdV-3

76

Calf

BAdV-7

103

Calves

BAdV-3

82

Lachrymation, nasal discharge, tympanitis, colic, diarrhoea

New-born calves

BAdV-3

81

Weak calf syndrome

Calves

BAdV-5

30

Calves

BAdV-5

25

Calves

BAdV-7

116

Reduced dietary nitrogen digestibility

Beef calves

BAdV-3

24

Enteritis

Ten-month-old bullock

Not determined

115

Seven to 18-months-old

NS

49

Cattle: two weeks

NS

19

Calves/steer

BAdV-3

123

Three-week-old calf

NS

94

Calves

BAdV-4

109

Systemic infection

Yearling heifer

BAdV-10

55

Pyrexia

Feeder calves

BAdV-3

82

Fatal enteric disease

Young calves

BAdV-10

114

Fatal haemorrhagic colitis

Young calves

BAdV-10

128

NS = Not stated

Enteric lesions are probably the result of endothelial necrosis (the cells often contain typical large intranuclear inclusions) in the vessels of the lamina propria and submucosa and may occur anywhere in the gastrointestinal tract from the rumen to the colon, but especially over the Peyer’s patches.5 These lesions result in the development of thrombi with resultant ischaemic necrosis of the dependent epithelium. Ulceration is a frequent consequence and a fibrinocellular exudate often covers the mucosal surface.5

Intranuclear inclusions may also occur in endothelial cells in the adrenals, mesenteric lymph nodes, liver, spleen, glomeruli and the capillaries in the interstitial tissues of the kidneys and in the mucosa of the urinary bladder.5

Diagnosis and differential diagnosis

Adenoviruses produce characteristic intranuclear inclusion bodies with margination of the chromatin. These may be recognized on histological examination of affected tissues.56, 96  Examination of such inclusions by transmission electron microscopy may reveal the characteristic adenovirus structure in virion arrays.56, 96

Bovine adenoviruses can readily be isolated from nasal and conjunctival swabs or faeces in bovine kidney, testis or thyroid cell cultures.9 A bovine thyroid cell line has been shown to support the replication of all bovine serotypes.14 Transformed foetal bovine retina cells also support BAdV-3 replication.101 It may be necessary to passage the material submitted for virus isolation several times before a cytopathic effect is obtained.

Serological tests usually rely on virus neutralization reactions or haemagglutination-inhibition (HI). The erythrocytes used in HI tests depend on the serotype involved; those obtained from rats are most commonly used.

Combination of different tests including electron microscopy, PCR, immunological tests  (virus neutralization, HI) and virus isolation can be helpful in diagnosis of BAdV infection.

Control

Vaccines against bovine adenoviruses have been produced,6, 20, 83, 119 but as the role of adenoviruses in cattle disease remains unclear, there is little justification for their use.119 A beneficial effect was demonstrated when an inactivated, aluminium hydroxide-adjuvanted vaccine was used in a herd in which pneumonia associated with BAdV 3 infection had been a severe problem.83

Adenovirus infections of sheep and goats

Introduction and aetiology

Infection of sheep with adenoviruses is probably ubiquitous and  most infections are subclinical, although a variety of clinical conditions have been associated with such infections. However, there is a stronger body of evidence implicating adenoviruses in the causation of respiratory tract disease in sheep than in cattle. In combination with other infectious agents, particularly Mannheimia (Pasteurella) haemolytica, they sometimes cause bronchopneumonia.

Seven ovine adenovirus (OAdV) serotypes are recognized in the Seventh Report of the International Committee for the Taxonomy of Viruses. While ovine serotypes 1-6 belong to the genus Mastadenovirus, ovine serotype-7  belongs to the genus Atadenovirus (Table 1).

Two adenovirus serotypes (GAdV) have been isolated from goats. GAdV-1 belongs to the genus Mastadenovirus, while GAdV-2 is assigned to the genus Atadenovirus (Table 1).

For the general characteristics of OAdV and GAdV see General Introduction: Adenoviridae and Aetiology of section of adenovirus infections of cattle.

Epidemiology

There is little information on the prevalence of adenovirus infections of sheep and goats  in different geographic locations or in various sex and age classes. Adenoviruses have been isolated from sheep in Northern Ireland, Britain, Turkey, New Zealand, Australia, Hungary and the USA.70, 96 However, not all sheep isolates are ovine adenoviruses as some from Hungary, Australia and New Zealand have been shown to be closely related, if not identical, to bovine serotypes 2 and 7.1, 10, 96 Antigenic relationship has been demonstrated among BAdV-6, BAdV-7, OAdV-7, GAdV-1, and deer (Odocoileus)  adenovirus 1 (OdAdV-1).75

A seroepidemiological study conducted in USA detected GAdV-1 reacting antibodies in 60 and 80 per cent of goat and sheep sera, respectively.71 A serological study conducted primarily in Iowa, USA, found that 95 per cent of ram lambs between one and four months of age had been infected with OAdV-5 and 42 per cent with OAdV- 6 viruses.72 In a subsequent serological survey for OAdV-1,-2,-3,-4 and BAdV-2, -3, and -7 using the virus neutralization test, approximately 45 per cent of the animals tested had neutralizing antibodies for at least one serotype, indicating that adenovirus infections were widespread in the sheep population.73

Adenovirus has been detected in the secretions of the upper respiratory tract of experimentally infected lambs for at least eight days after infection69 and such virus-laden secretions probably transmit the infection during close contact between infected and susceptible individuals. The faecal–oral route is probably also important,87 although no virus could be detected in faeces in some experimental infections.69, 70 Excretion lasting at least 80 days has been claimed.110 Transplacental transmission has been demonstrated.12

Pathogenesis

Several studies indicate that ovine adenoviruses (in addition to other viral infections of the respiratory tract, such as respiratory syncytial virus and parainfluenza type 3) act synergistically with M. haemolytica to cause serious bronchopneumonia.11, 29, 66, 70 The consensus appears to be that adenovirus infections are relatively mild but that they predispose to colonization of the lungs by M. haemolytica as they impair the bacterial clearance mechanisms.

It appears that adenoviruses replicate in the epithelial cells of the airways, except possibly those of the alveolar epithelium.28 In an experimental model in which a human adenovirus (h5) was used to induce respiratory disease in cotton rats (Sigmodon hispidus), it was shown that type II alveolar cells supported only an incomplete replicative cycle of the virus.99

Clinical signs and pathology

Most adenovirus infections in sheep are subclinical.8, 31, 33, 70, 87 Serious respiratory disease, particularly bronchopneumonia, has been ascribed to adenoviruses, usually in association with other viral and secondary bacterial infections.11, 29, 32, 66, 68 Lung lesions, as in the case of cattle, are characterized by proliferative and necrotizing bronchiolitis, with some epithelial cells containing typical intranuclear inclusions. Some of the cells bearing inclusions have markedly enlarged nuclei and cytoplasm.41

Goat adenovirus-1 has been isolated from an adult goat with encephalitis71 and GAdV-2  from the  small intestine of a three- week-old neonatal goat with diarhoea and ocular/nasal discharges74 However, the role of GAdVs in respiratory and enteric disease in goats has not been clearly established yet.

An unusual outbreak of liver haemorrhage and hepatocyte necrosis associated with adenovirus infection in Merino wethers and ewes has been described in Australia.96 However, these animals also had lesions consistent with cycad poisoning. In a number of independent experimental infections no virus was found in liver,69, 70 except for one instance.107

Two outbreaks of pneumo-enteritis associated with adenovirus infection were described among lambs on large scale farms in Germany.11 Numerous adenovirus isolates were made from affected lambs that also showed rises in virus neutralizing antibody titres between acute and convalescent phase sera. Vaccine produced from one of the viruses involved provided measurable protection against experimental and field challenge. Focal interstitial pneumonia, affecting mainly the ventral parts of the apical, cardiac and accessory lobes, characterized infections that were not accompanied by secondary bacterial infection. Secondary infection induced croupous or chronic catarrhal pneumonia. Some bronchi showed epithelial hyperplasia. Pathological changes in the kidneys and lymph nodes of the respiratory tract were also described.11

Ovine adenovirus-7 has been associated with  death of neonatal lambs in the USA36 characterized by multifocal necrotizing hepatitis, subacute interstitial nephritis and loss of enterocytes from intestinal villi. Adenovirus inclusions were detected by light microscopy. Ovine adenovirus-7 may also play a role in  ovine pneumonia.32 A consistent finding in experimentally induced respiratory disease caused by adenoviruses has been proliferative bronchiolitis, which may progress to bronchopneumonia. Basophilic intranuclear inclusion bodies were sometimes visible in swollen epithelial cells, while cytomegaly and karyomegaly occurred in some cells containing inclusions.28, 29, 31, 32, 125

Diagnosis and control

Ovine adenoviruses have been isolated using primary lamb kidney cells (LK), Madin–Darby bovine kidney (MDBK) cells, ovine foetal turbinate cells,36 or sheep foetal lung cell line (CSL 503),17 and goat adenoviruses using foetal turbinate cells.36 Transmission electron microscopy can also be used to detect these viruses in specimens.

The routine use of vaccines against ovine adenovirus infections has not been described, but specially formulated vaccine may be beneficial in particular problem situations.6, 11, 95

Adenovirus infections of pigs

Introduction and aetiology

Most adenovirus infections of pigs are subclinical, but some strains may cause abortion, enteric or respiratory disease and in rare instances, meningoencephalitis.127 The pathogenicity of porcine adenovirus (PAdV) infection may be increased by co-infection with other agents.

Five PAdV serotypes (PAdV-1 to 5) belonging to Mastadenovirus  are recognized. Recently, two more strains of PAdVs  (PAdV- WI and PAdV-SVN1) have been isolated, which may represent  new species.58, 112 Porcine adenovirus-4 is the most common serotype in pigs.127

Epidemiology

Adenovirus infections of pigs are ubiquitous as they have been identified in the UK, Belgium, Germany, Australia, Canada, Japan, and the USA.15, 35, 52, 60, 62, 65, 93, 108 So far PAdVs have been isolated from healthy animals, pigs showing signs of gastrointestinal disease, nasal secretions of pigs manifesting signs of respiratory disease, and aborted and stillborn piglets.13, 97

Infection rates may be high (seropositivity rates of up to 50 per cent have been observed)15  and infection may occur in piglets less than three weeks of age,108 and therefore possibly in the presence of maternally-derived antibody. However, infection may be acquired transplacentally prior to the acquisition of maternal antibody by piglets,62, 93 but the frequency with which this occurs is unknown.

Horizontal transmission between pigs presumably occurs by the faecal–oral route or by the transfer of virus containing oronasal secretions during close contact. Respiratory and enteric infections have been experimentally reproduced.27, 108 Adenovirus inclusion bodies have been shown to persist for at least 15 days in enterocytes of the lower small intestine and it is possible that alimentary excretion of PAdVs occurs for longer than is usual in other viruses that infect the porcine gastrointestinal tract.40 Excretion in faeces is probably heaviest in pigs for a short while after weaning; adult pigs rarely excrete adenoviruses in their faeces.38

Pathogenesis, clinical signs and pathology

Piglets younger than four weeks  are most susceptible. The most consistent clinical sign observed is yellowish diarrhoea that lasts for about a week. Infected animals may show  depression, emaciation and dehydration.13, 97, 127

Transplacental infection in porcine foetuses may result in widespread infection of the endothelial cells of the capillaries and small blood vessels throughout the body,93 resulting in cyanosis of the skin and oedema of the subcutaneous tissues at birth. Inclusions in the nuclei of endothelial cells of the infected piglets are most plentiful in the liver, spleen, kidneys and lymph nodes.93 Porcine adenovirus infection has also been implicated on rare occasions as a cause of  abortion.62

More commonly, PAdVs have been associated with the respiratory and/or gastrointestinal tracts of pigs infected after birth, but their involvement in the causation of disease is problematic as they can frequently be recovered from healthy animals.18, 34, 108 However, some PAdVs regularly cause respiratory and enteric disease when administered to susceptible pigs.27, 40 Porcine adenovirus-4  has been shown to be a cause of meningoencephalitis in piglets.43, 60

The intestine is probably the primary site of infection, the tonsils, for example, being infected more sporadically and at a later stage than the intestine, probably following viraemic spread.40 Both villus and crypt enterocytes, as well as goblet cells, are infected in villi that are severely shortened.97, 127 There is a predilection for the enterocytes that cover the short villi of the terminal parts of the jejunum and ileum, particularly those that cover lymphocytic aggregates in which typical adenovirus intranuclear inclusions occur.18, 27 This differs from the situation in cattle, where the inclusions occur in endothelial cells of vessels in the lamina propria and submucosa.4 Intranuclear inclusions have also been described in epithelial cells of the tonsils and capillary endothelial cells.97, 127

Porcine adenoviruses appear to have less affinity for pulmonary epithelium than is the case with BAdV or OAdV but have been associated with interstitial pneumonia and occasionally with encephalitis.97, 127

As is the case with adenovirus infections in sheep and cattle, it is likely that co-infection with other agents increases the pathogenicity of adenoviruses. Such synergistic action has been demonstrated between PAdV- 4 and Mycoplasma hyopneumoniae,61 although not between PAdV- 4 and Pasteurella multocida.113

Diagnosis and control

Diagnosis includes viral isolation in porcine thyroid cells and  transformed porcine retina cells,102 detection of antibodies with immunodiffusion, complement fixation, serum neutralization and ELISA, and microscopic demonstration of intranuclear inclusion bodies in the intestinal cells. Detection of viral particles with transmission electron microscopy or viral antigens using techniques such as immunoperoxidase and immunofluorescent staining or virus specific PCR or qPCR may also be useful. An increase in antibody titre together with clinical signs is suggestive of clinical disease.13, 97

There are no reports of attempts to control adenovirus infections in pigs. Applying good sanitation practices that reduce environmental faecal contamination13 could prevent transmission of the virus. While PAdV survive in the environment for a prolonged period of time, they are susceptible to commonly used disinfectants.

Adenovirus infections of horses

Introduction and aetiology

The vast majority of equine adenovirus (EAdV)  infections are clinically inapparent, although association with respiratory disease has been claimed. These horses shed virus and remain  carriers. In Arabian foals suffering from the inherited combined immune deficiency syndrome, pneumonia caused by EAdV infection is usually the immediate cause of death.

Although the original studies on the possible antigenic diversity of EAdV isolates found little variation,21, 46, 121 subsequent studies have indicated that there are at least two serotypes (EAdV-1 and EAdV-2)  belonging to the genus Mastadenovirus.54, 120

Epidemiology

Antibodies to EAdVs have been identified in horse sera in many countries in Europe, Asia and North America as well as in Australia and New Zealand, indicating that they are probably ubiquitous.53 Not only is the geographic distribution of EAdVs wide, but antibodies against them have been found in all the horse breeds in which a significant number of animals have been serologically tested.53 Prevalence rates are usually higher than 70 per cent in adult horses,53, 121 although in some groups of horses under the age of one year, 50 per cent or more are seronegative.121

The observation has been made that EAdV infection was able to persist in a small pony herd that was maintained in relative isolation.21 This indicates that prolonged, possibly intermittent, virus excretion occurs. Transmission is presumably dependent upon direct contact with the respiratory secretions, or perhaps faeces, of infected horses.

Pathogenesis, clinical signs and pathology

Equine adenovirus-1 and EAdV-2  are transmitted through nasal and oral routes, respectively and new-born foals may be infected by their mothers. Equine adenovirus-1 replicates in the epithelial cells of respiratory tract whereas EAdV-2 replicates in the epithelial cells of the gastrointestinal tract. Moreover, EAdV-1 containing nasal and ocular discharges, and EAdV-2 containing faecal materials are responsible for the spread of the infections from one animal to the other.

Most EAdV infections are inapparent and it is generally accepted that they are not important as a cause of upper respiratory tract disease in racehorses.98 Infection may, however, cause mild upper respiratory tract disease in foals,42, 59, 86 especially, it is postulated, in the presence of other infectious agents.21 They have also been associated with diarrhoea in foals26, 120 and cauda equina neuritis.44 


The most commonly reported clinical condition associated with EAdV infection is pneumonia, which occurs in young (10 days to three months of age) Arabian foals afflicted with the combined immune deficiency syndrome.85, 86, 88, 122. This syndrome is inherited via a simple recessive autosomal gene and the inability of affected animals to withstand infection invariably leads to a fatal outcome.122 It is diagnosed in about 2 per cent of Arabian foals.129

In immunodeficient foals, clinical signs develop two to six weeks after birth. Clinically, affected foals have fever that may be intermittent, mucopurulent nasal and ocular discharges, dyspnoea, bronchial râles and sometimes a cough. Because the course of the disease is between 13 and 42 days, foals in the advanced stages of the disease may be in poor condition.84, 86, 122 They may also suffer from dermatitis due to dermatophilosis and other concurrent infections.122

B-lymphocyte deficiency in these foals is indicated by an absolute lymphopenia, hypogammaglobulinaemia in which IgM and IgA are usually undetectable while IgG and IgG(T) are present in lower than normal concentration, and absence of germinal centres in the spleen and lymph nodes.88 T-lymphocyte deficiency is shown by the absence of thymus tissue and peri-arteriolar lymphocytic sheaths in the spleen.88 The lymph nodes are smaller than normal.85 Neutropenia also occurs.84

Macroscopically, the lungs lesions consistent of areas of atelectasis and pneumonia, while microscopically there is swelling, hyperplasia and necrosis of the respiratory epithelium throughout the respiratory tract, and some cells contain typical intranuclear inclusion bodies.85, 86 In some instances the pneumonia has been described as interstitial, and secondary bacterial infection has resulted in the development of bronchopneumonia.88

Epithelial lesions similar to those of the respiratory tract have also been observed microscopically in the transitional epithelium of the renal pelvis, ureters, bladder and urethra as well as conjunctival epithelium, ductal and parenchymatous epithelium of the lachrymal glands, salivary glands, pancreas and tubuloacinar glands. In a minority of cases small groups of epithelial cells in the intestinal tract may be swollen, contain intranuclear inclusion bodies and undergo necrosis.85

Diagnosis and control

Apart from primary and low-passage kidney cells,  EAdVs can be cultured in MDCK (canine kidney), MDBK (bovine kidney)57 and BS-c-1124  cells. The virus neutralization test is the gold standard used for differentiating EAdV-1 and EAdV-2. PCR and transmission electron microscopy have been used to detect virus or viral antigen in faecal samples. Gross and histopathological lesions in infected tissues of the respiratory tand gastrointestinal tracts are also important for EAdV diagnosis.
Because equine EAdVs are not important in the causation of disease in horses that are unaffected by the combined immune deficiency syndrome, no specific control measures have so far been deemed necessary. An experimental vaccine containing virus inactivated by application of a combination of ultraviolet radiation and β-propiolactone has been described.78 This vaccine induces  high antibody levels in foals.

Although adenoviral infection that complicates the combined immune deficiency syndrome in Arabian foals is almost invariably fatal, beneficial effects have been obtained in affected animals by administering antibiotics and antisera or whole blood with high antibody levels against EAdV.85

Adenovirus infections of other species

Although this chapter deals with adenovirus infections in livestock, those in others animal species are briefly discussed here.

Adenovirus infection of deer

The Odocoileus deer adenovirus (OAdV) that causes adenovirus haemorrhagic disease (AHD) in cervids (mule deer, white-tailed deer, moose, elk and pronghorn) belongs to the genus Atadenovirus.111, 135 Outbreaks of AHD leading to high mortality in cervids have been recorded in different parts of USA.16, 134 The complete genome sequence of OAdVs isolated from different cervid species appears to be highly conserved.90 Recently, a novel adenovirus designated cervid adenovirus1 (CeAdV-1) was isolated from a healthy white-tailed deer, Odocoileus virginianus.104 Based on viral DNA sequence and phylogenetic analysis, CeAdV-1was classified as member of Mastadenovirus.104

Odocoileus deer adenovirus-1 has been linked with large-scale epidemics in mule deer (Odocoileus hemionus) in North America.134 A recent study reported that 38.4 per cent of mule deer in south-eastern British Columbia, Canada were seropositive for OdAdV-1 antibodies. Exposure was found to be age dependent.80 The virus is transmitted via direct contact among deer and indirect contact with bodily fluid.  Odocoileus deer adenovirus -1 affects deer of all ages and both sexes, but mortality is more pronounced in fawns. The AHD cases are mostly observed in summer. So far, there are no reports that OAdV-1 can infect other species.

Serological surveys detected high levels of  CeAdV-1 specific antibodies in captive white-tailed and free ranging mule deer, suggesting that virus has been circulating in deer herds for the last 15 years.104

Clinical signs of AHD include open mouth breathing, drooling of saliva, weakness and death occurs within a week of exposure to the acute form of the disease. The chronic form of the disease is characterized by the appearance of lesions in the throat and oral cavity.132

Gross lesions include erosions, ulcers, haemorrhages, and abscesses in the upper digestive tract and systemic vasculitis, in particular affecting the lungs and leading to pulmonary oedema. Histologically, intranuclear inclusion bodies can be detected in the endothelial cells.16, 134

Experimental infection of white-tailed deer fawns with CeAdV-1 resulted in mild respiratory disease, pyrexia, and depletion of  thymus tissue.104

Since gross and histological lesions are similar to bluetongue (see Bluetongue) and epizootic haemorrhagic disease (see Epizootic haemorrhagic disease) various laboratory tests can be used to make a diagnosis.132

There is no vaccine or treatment available for AHD. Measures that help to limit spread of the disease include proper carcass disposal, restriction of infected deer movement and proper handling of infected deer.132

Canine adenovirus infections

Canine adenoviruses (CAdVs) are endemic in domestic dogs and can cause severe disease in dogs, wolves, jackals, foxes and coyotes.37 Two  serotypes (CAdV-1 and CAdV-2) belonging to the genus Mastadenovirus have been described. Canine adenovirus-1 infects members of three  families: Canidae (dogs, wolves), Ursidae (bears) and Mustelidae (skunks and otters). It causes infectious canine hepatitis (ICH),23 a contagious systemic disease in domestic dogs, formerly known as epizootic encephalitis of foxes. Subclinical CAdV-1 infections are common among wild canids, that can be the potential source of sporadic ICH in unvaccinated domestic dogs. Canine adenovirus-2 infections are common among kennelled dogs and cause canine infectious tracheobronchitis (CIT), or kennel cough syndrome (KCS), a mild upper respiratory disease.51 Due to high antigenic relatedness, CAdV-1 and CAdV-2 are cross-protective in infected animals.

Canine adenovirus can be transmitted by direct contact of virus-contaminated faeces, urine, saliva or nasal discharges and ectoparasites133 or by contact between animals.

Although modified live and killed vaccines are commercially available, modified live attenuated vaccines provide lifelong immunity. CAdV-1 vaccines have been removed globally because it causes blue eye (corneal oedema) in dogs. Only CAdV-2 vaccines are today used globally for the vaccination of dogs.

References

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