Canine Adenovirus 1

Introduction

Canine Adenovirus 1 (CAV-1) was first isolated by Carbasso in 1954¹ from a case of acute hepatitis in the dog. This virus found to be identical to the virus isolated in 1947 by Rubarth² from a dog showing acute liver lesions, and so CAV-1 was originally known as Infectious Canine Hepatitis (ICH) virus. Subsequently, CAV1 infection was shown to be common in young dogs worldwide, with 82% of British dogs displaying neutralising antibody titres by nine months of age³. It has also since been demonstrated that CAV1 has a role in diseases other than Infectious Canine Hepatitis, such as Canine Infectious Tracheobronchitis.

Classification

CAV-1 is a member of the Adenoviridae family, a group double-stranded DNA viruses with an icosahedral nucleocapsid. Many Adenoviridae have been isolated from mammals and birds, but only a small number of these cause significant veterinary disease. The family consists of four genera: Mastadenovirus, Aviadenovirus, Atadenovirus and Siadenovirus. Canine adenovirus 1 is a Mastadenovirus.

Viral Characteristics

The genetic information of CAV-1, like other Adenoviridae, is conveyed by a single, linear molecule of double-stranded DNA which encodes around 30 proteins. Under the influence of both host and virus-encoded factors, the DNA replicates and is transcribed within the host nucleus, where virion assembly also occurs. Basophilic and/or acidophilic inclusions may therefore be seen in the nucleus of an adenovirus-infected cell.

The virus genome is contained within a non-enveloped icosohedral nucleocapsid, which comprises capsomeres (called hexons) and twelve vertex capsomeres (called pentons). A fibre antigen protrudes from each of the twelve pentons, and this attaches to host cell receptors as well as being a type-specific haemagglutinin. This fibre antigen is a feature specific to the Adenoviridae. The hexon of mammalian adenoviruses contains a cross-reacting group antigen.

Hosts

Young dogs are most most commonly infected with canine adenovirus 1, but disease is uncommon where vaccination is practiced. Wild and captive foxes may contract the virus leading to fox encephalitis, and wolves, coyotes and bears can also become clinically infected. Subclinical infections can arise in other carnivores.

Transmission and Epidemiology

CAV-1 infection occurs by inhalation and ingestion, after shedding in the urine, faecs or respiratory secretions. Transmission my be by direct contact, or by indirect contact and fomites such as handlers or infected surfaces. Following infection, the virus initially replicates in the tonsils and Peyer's patches. A viraemia is produced, and CAV-1 secondarily localises and replicates in the liver and kidneys.

Clinical Features

Although there is evidence for a high incidence of infection among the non-vaccinated canine population, this is not matched by a similar occurance of clinically detectable infectious hepatitis since many infections are subclinica. The virus has also been show to be involved in several other types of disease. These include encephalopathy ⁴, ocular lesions, neonatal disease⁵, chronic hepatitis⁶, and interstitial nephritis⁷. The virus can be isolated from throat swabs or lungs fro some dogs with respiratory disease, and CAV-1 is of importance in Canine Infectious Tracheobronchitis.

In Infectious Canine Hepatitis, clinical signs typically include depression, fever, vomiting, diarrhea, and discharges from the nose and eyes. Coagulopathies may also develop.

Pathology

Infection with canine adenovirus 1 most typically causes a mild bronchointerstitial pneumonia, although a necrotising bronchiolitis may occur in immunocompromised dogs. This is seen histologcally as necrosis of the bronchiolar and alveolar epithelium, pulmonary oedema and hyperplasia of type II pneumocytes.

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The principal tissue changes involve the endothelium and hepatic cells. Damaged endothelium results in widespread petechial hemorrhages. The liver may be enlarged or normal in size, but usually is mottled because of focal areas of necrosis. Microscopically, the most significant changes are found in the liver, where centrolobular necrosis is noted and typical adenoviral inclusion bodies are observed in Kupffer cells and parenchymal cells. Circulating immune complexes in the glomeruli may result in glomerulonephritis. Recovered dogs may develop a transient corneal opacity ("blue eye") as a result of local immune complex deposition. Recovery from infectious canine hepatitis (ICH) results in lasting immunity. Diagnosis Clinical specimens: liver, spleen, kidney, blood, urine, nasal swabs and paired serum samples. Diagnosis of ICH is usually made on the basis of clinical signs and gross and microscopic lesions including the presence of basophilic inclusions in hepatocytes, endothelial cells, and Kupffer cells. The virus can be demonstrated in frozen liver sections by immunofluorescence. The virus can be cultivated in cell cultures of canine origin. The liver has been reported to be less suitable for virus recovery than other vital organs. A rising titer of antibodies employing hemagglutination inhibition or virus neutralization are supportive of a diagnosis. Prevention Modified live and killed vaccines are used, often in combination with parvovirus and canine distemper antigens. Modified live vaccines induce a longer lasting immunity, but a small percentage of vaccinated dogs may develop ocular or renal lesions. These core canine vaccines were traditionally administered annually but are now, depending on the type of vaccine, often given less frequently.

References

1. Rubarth, S (1947) An acute virus disease with liver lesions in dogs (heptatitis contagiosa canis). Acta Path Microbiol Scand, Supplement 67
2. Carbasso, VJ et al (1954) Propagation of infectious canine hepatitis virus in tissue culture. Proc Soc Exp Biol Med, 85
3. Ablett, RE and Baker, LA (1960) The development in the dog of naturally acquired antibody to canine hepatitis in relation to age. The Veterinary Record, 72
4. Koptopoulos, G and Cornwell, HJC (1981) Canine adenovirusees: a review. The Veterinary Bulletin, 51(3)
5. Carter, GR and Wise, DJ (2005) A Concise Review of Veterinary Virology, International Veterinary Information Service.

Adenovirus pneumonia (Image sourced from Bristol Biomed Image Archive with permission)