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

Canine adenovirus 1 (CAV1) is a member of the Adenoviridae family. The Adenoviridae are a family of double-stranded DNA viruses which have an icosahedral nucleocapsid and have been isolated from many mammals and birds. However, only a small number of Adenoviridae cause significant veterinary disease, one of these being canine adenovirus 1. Classification This family originally consisted of only two genera, Mastadenovirus, which infect mammals, and Aviadenovirus, which infect birds. There are also several as yet unassigned and recently assigned viruses in the family. Mastadenovirus This genus consists of 20 virus species that infect mammals including canine, equine, bovine, ovine and porcine adenoviruses. All 20 species share a common antigen. Important diseases are infectious canine hepatitis, canine adenovirus 2 infection, and equine adenovirus A infection. Aviadenovirus This genus includes the viruses of inclusion body hepatitis, quail bronchitis, marble spleen disease and a number of adenoviruses of poultry and birds that are not associated with significant diseases. Members of the genus share a common antigen. Previously Unassigned Adenoviruses Included in this category are the viruses that have recently (2002) been placed in the genera Atadenovirus and Siadenovirus. These viruses include the egg drop syndrome virus (Atadenovirus), turkey hemorrhagic enteritis (Siadenovirus), adenoviral splenomegaly of chickens (Atadenovirus) and ovine adenovirus 287 (Atadenovirus; of research interest, but of no disease significance) and some bovine adenovirus types 4 to 8 (Atadenovirus). MastadenovirusInfectious Canine HepatitisCause Canine adenovirus 1. The DNA sequence of this virus has been determined.

Viral Characteristics

Non-enveloped, viruses with icosahedral symmetry containing a single, linear molecule of double-stranded DNA.

The capsid consists of capsomeres (called hexons) and 12 vertex capsomeres (called pentons). These are the only viruses with a fiber (the fiber antigen) protruding from each of the 12 pentons (see Fig. 13-1). The fiber is the structure of attachment to host cells and is also a type specific hemagglutinin. The hexon of mammalian adenoviruses contains a cross-reacting group antigen. The fiber antigen attaches to a specific cell receptor and initiates replication. The dsDNA encodes approximately 30 proteins. Viral DNA replication, mRNA transcription and virion assembly occur in the nucleus, utilizing both host and virus-encoded factors. This results in the formation of basophilic and / or acidophilic intranuclear inclusions. Many adenoviruses agglutinate red cells of various animal species and some are capable of malignant transformation in tissue culture cell and oncogenesis when inoculated into laboratory animals. They are resistant to trypsin and lipid solvents, and moderately resistant on premises. Figure 13-1. Adenoviridae (70 - 90 nm). Note the fiber proteins protruding from the vertices of the 12 pentons. To view click on figure

Hosts

• Dogs
• Foxes are very susceptible (Fox Encephalitis)

Occurrence Dogs younger than one year of age are most often affected. The virus also infects wild and captive foxes causing encephalitis, and wolves, coyotes and bears. Other carnivores may sustain subclinical infections. The disease occurs commonly worldwide, but is uncommon where vaccination is practiced.

Transmission and Epidemiology

• Transfers easily via ingesting infected urine, feces or respiratory secretions
• Can be transferred by handlers, infected surfaces, etc

Infection is by inhalation and ingestion. Spread is by direct and indirect contact.

The virus replicates initially in tonsils and Peyer’s patches producing a viremia with secondary localization and replication in the liver and kidney .

Disease

This high incidence of infection is not matched by a similar incidence of clinical hepatitis, and it si now known that many infections are subclinical and that the virus is also responsible for other conditions, e.g. encephalopathy, ocular disease, neonatal disease, chronic hepatitis, and interstitial nephritis. In several countries, the virus has been isolated from throat swabs or lungs from dogs with respiratory disease, and in Britain CAV-1 is thought to be of importane in kennel cough (infectious tracheobronchitis).

Clinical signs include depression, fever, vomiting, diarrhea, and discharges from the nose and eyes. Because of a tendency to bleed, hematomas may be seen in the mouth.

• Adenoviridae
• Usually mild bronchointerstitial pneumonia, necrosis of bronchiolar and alveolar epithelium, oedema, type II pneumocyte hyperplasia
• May cause necrotising bronchiolitis in immune-deficient dogs (distemper)
• Can be associated with kennel cough described ab

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

• Koptopoulos, G and Cornwell, HJC (1981) Canine adenovirusees: a review. The Veterinary Bulletin, 51(3)
• Rubarth, S (1947) An acute virus disease with liver lesions in dogs (heptatitis contagiosa canis). Acta Path Microbiol Scand, Supplement 67
• Carbasso, VJ et al (1954) Propagation of infectious canine hepatitis virus in tissue culture. Proc Soc Exp Biol Med, 85

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