71       Caliciviridae

 

Caliciviruses (Latin calix, cup) have cup-shaped depressions on the surface of virions, demonstrable by electron microscopy. The virions, 27 to 40 nm in diameter, are icosahedral and non-enveloped. The genome consists of a single molecule of linear, positive-sense, single-stranded RNA. Replication takes place in the cytoplasm of infected cells and virions are released by cell lysis. Many caliciviruses have not yet been cultured. The virions are resistant to ether, chloroform and mild detergents. They are relatively resistant to heat but are sensitive to acid pH values.

The family Caliciviridae is divided into five genera: Vesivirus, Lagovirus, Nebovirus, Sapovirus and Norovirus. Caliciviruses belonging to the Norovirus and Sapovirus genera include viruses which cause acute gastroenteritis in humans.

Clinical infections

Caliciviruses have been recovered from many species including humans, cats, pigs, marine mammals, fish, rabbits, hares, cattle, dogs, reptiles, amphibians, shellfish and insects. They are associated with a wide range of conditions including respiratory disease, vesicular lesions, necrotizing hepatitis and gastroenteritis (Table 71.1). Infections with caliciviruses, which are frequently persistent, may be inapparent, mild or acute. Transmission occurs directly or indirectly without vector involvement. However, mechanical transmission of rabbit haemorrhagic disease virus by mosquitoes and fleas has been described.

Table 71.1 Caliciviruses of veterinary importance.

Virus	Hosts	Comments
Vesicular exanthema of swine virus	Pigs	Acute, contagious vesicular disease, clinically similar to foot-and-mouth disease. Occurred in the USA before 1956. May have arisen from feeding sea lion and seal meat contaminated with San Miguel sea lion virus
San Miguel sea lion virus	Marine mammals, opal eye fish	Associated with cutaneous vesicles and premature parturition in pinnipeds; when inoculated into pigs, causes vesicular exanthema
Feline calicivirus	Domestic and wild cats	Important cause of upper respiratory tract infection in cats worldwide. Virulent systemic disease described in some outbreaks
Rabbit haemorrhagic disease virus	European rabbits	Acute fatal disease in European rabbits over 2 months of age
European brown hare syndrome virus	European brown hares	Related to rabbit haemorrhagic disease virus. Causes hepatic necrosis and widespread haemorrhages with high mortality
Canine calicivirus	Dogs	Occasionally associated with diarrhoea
Newbury-1 virus	Cattle	Has been linked to diarrhoea in calves

Feline calicivirus infection

Infections caused by feline calicivirus (FCV) account for about 40% of upper respiratory tract inflammatory disease in cats worldwide. All species of Felidae are considered to be susceptible but natural disease tends to be confined to domestic cats and to cheetahs in captivity. There is a high degree of antigenic heterogeneity among FCV isolates. Sequence analysis studies have shown that individual isolates of FCV exist as quasispecies which evolve and exhibit antigenic drift. Significant alterations in the antigenic profiles of sequential virus isolates from carrier cats are thought to be influenced by immune selection and this may play an important part in viral persistence.

Virus replication occurs primarily in the oropharynx with rapid spread throughout the upper respiratory tract and to the conjunctivae. A transient viraemia occurs. Infections range from subclinical to severe, reflecting differences in strain virulence and host immunity. Virulent strains of FCV can cause interstitial pneumonia in young kittens. The virus has been recovered from the joints of lame cats. Highly virulent strains of the virus associated with virulent systemic disease (VSD) have been reported periodically.

The incubation period is up to five days. Clinical signs, which are usually confined to the upper respiratory tract and the conjunctivae, are often less severe than those caused by feline herpesvirus 1 infection. Fever, oculonasal discharge and conjunctivitis are accompanied by the development of characteristic vesicles on the tongue and oral mucosa. These vesicles rupture leaving shallow ulcers. Morbidity may be high but mortality is usually low. Stiffness and shifting lameness, which usually resolve within a few days, are sometimes seen during the acute phase of FCV infection or following inoculation with FCV vaccine. The VSD form of FCV infection is characterized by severe upper respiratory tract disease, facial oedema, ulceration of the skin, vasculitis, multi-organ involvement and high mortality.

Although cats of all ages are susceptible to infection with FCV, acute disease occurs most commonly in kittens as maternally derived antibody wanes between two and three months of age. Infected cats excrete large amounts of virus in oronasal secretions. Many cats continue to shed virus continuously from the oropharynx for weeks after recovery from acute infection or following subclinical infection while protected by maternally derived antibody or by response to vaccination. A minority of cats shed virus for months and, occasionally, for years. Infection is maintained in the cat population by these asymptomatic FCV carriers. The highest prevalence of infection is seen in large groups of cats living in colonies or shelters.

Due to the similarity of clinical signs caused by infection with feline herpesvirus 1 and FCV, laboratory tests are required to differentiate these two diseases. Feline calicivirus can be isolated in feline cell lines from oropharyngeal swabs or from lung tissue. Viral RNA can be detected in clinical specimens using RT-PCR. However, detection of FCV may not be aetiologically significant in every instance because of the presence of carrier animals in cat populations. Demonstration of a rising antibody titre in paired serum samples is required for laboratory confirmation.

Vaccination and management practices aimed at reducing exposure to the virus are the main methods of control. Inactivated vaccines for parenteral administration and modified live vaccines for either parenteral or intranasal administration are available. Although vaccination protects effectively against clinical disease in most instances, it does not prevent subclinical infection or the development of a carrier state. Vaccines are based on a limited number of FCV isolates which cross-react with a broad spectrum of field isolates. Live vaccines, for administration by injection, may cause clinical signs of disease if given by other routes.

Rabbit haemorrhagic disease

This is a highly contagious, acute and often fatal disease of European rabbits (Oryctolagus cuniculus). Rabbit haemorrhagic disease (RHD) was first reported in China in 1984 and has since been encountered in many parts of the world. This virus is considered to be a mutant form of a non-pathogenic virus, termed rabbit calicivirus, which has been endemic in commercial and wild rabbits in Europe for many years. Rabbit haemorrhagic disease virus (RHDV) has been used for biological control of rabbits in Australia and New Zealand.

Virus is shed in all excretions and secretions. Among rabbits in close contact, transmission is mainly by the faecal–oral route. Infection may also occur by inhalation or through the conjunctiva. Mechanical transmission by a variety of insects, including mosquitoes and fleas, has been demonstrated. The virus survives in the environment and indirect transmission through contaminated foodstuffs or fomites may occur.

Cells of the mononuclear phagocyte lineage are considered to be the major targets of the virus. Rabbits under two months of age do not develop clinical signs. The reason for this resistance is unclear, but it may have a physiological basis. Severe hepatic necrosis is the most obvious lesion in affected rabbits. In addition, there may be evidence of disseminated intravascular coagulation.

The incubation period is up to three days. The disease is characterized by high morbidity and high mortality. The course is short, with death occurring within 36 hours of the onset of clinical signs. Rabbits may be found dead or die in convulsions. A few rabbits may present with milder, subacute signs during the later stages of a major outbreak.

High mortality in rabbits along with characteristic gross lesions including necrotic hepatitis and congestion of spleen and lungs are suggestive of RHD. Culture of RHDV has been unsuccessful. High concentrations of virus are present in affected livers. Confirmation is based on detection of virus by electron microscopy or of viral antigen by ELISA, immunofluorescence or haemagglutination using human erythrocytes. Reverse transcriptase PCR has been developed for the detection of RHDV nucleic acid. Suitable serological tests for the detection of specific antibodies to the virus include haemagglutination-inhibition and ELISA.

In countries where RHD is endemic, control is achieved by vaccination. Inactivated and adjuvanted vaccines are available. A live myxoma virus expressing the capsid protein gene of RHDV is available for the vaccination and protection of rabbits against both viruses.