66       Paramyxoviridae

 

Paramyxoviruses and orthomyxoviruses were formerly grouped together as the ‘myxoviruses’ (Greek myxa, mucus), a name which describes their affinity for mucous membranes. Paramyxoviruses are pleomorphic, 150 nm or more in diameter and enveloped. They contain a single molecule of negative-sense, single-stranded RNA. Two types of glycoprotein ‘spikes’ or peplomers are present in the envelope, an attachment protein and a fusion protein (F). The attachment protein may be either a haemagglutinin–neuraminidase protein (HN) or a protein without neuraminidase activity (G or H). The attachment proteins allow the virus to bind to cell surface receptors and the fusion protein causes the virus envelope to fuse with the host cell membrane. However, there is significant variation between different paramyxoviruses in the mechanism of viral attachment, stimulation of the fusion protein and the process of viral entry into the cell. Both types of peplomers can induce production of virus neutralizing antibodies. Paramyxoviruses may exhibit haemagglutinating, haemolytic and neuraminidase activities. The nucleocapsid, which has helical symmetry, is 13 to 18 nm in diameter and has a characteristic herring-bone appearance. Replication occurs in the cell cytoplasm and acidophilic inclusions are a feature of paramyxovirus infections. Virions are released by budding from the plasma membrane at sites containing virus envelope proteins. The labile virions are sensitive to heat, desiccation, lipid solvents, non-ionic detergents and disinfectants.

The family is divided into two subfamilies, Paramyxovirinae and Pneumovirinae, containing seven and two genera respectively. The genera Aquaparamyxovirus (viruses of fish) and Ferlavirus (viruses of reptiles) are the most recent members of the family to be designated as genera in a family that continues to expand as new virus species in wild animals are discovered. Although paramyxoviruses are genetically relatively stable and do not appear to undergo recombination, some antigenic variation occurs through mutational changes and selection.

Clinical infections

Paramyxoviruses, which typically have a narrow host range, infect mainly mammals and birds (Table 66.1). Following transmission through close contact or by aerosols, replication occurs primarily in the respiratory tract. Disease outbreaks of viral infections in marine mammals has led to the recognition of new morbilliviruses, phocine distemper virus and cetacean morbillivirus. Fruit bats are the reservoir hosts of the zoonotic henipaviruses. Hendra virus was isolated during an outbreak of severe respiratory disease in horses in Australia during 1994. Two humans in contact with infected horses were also affected; 14 horses and their trainer died. A related virus, Nipah virus, was isolated in Malaysia during 1999 following outbreaks of disease in pigs and humans working in affected pig units. The disease, which caused a febrile encephalitis, resulted in more than 100 human deaths. New paramyxoviruses continue to be identified in bats, particularly fruit bats, including Menangle virus, Tioman virus, Mapuera virus and bat parainfluenza virus. Menangle virus and Tioman viruses can produce disease in pigs, while Mapuera virus is closely related to porcine rubulavirus.

Table 66.1 Paramyxoviruses of veterinary importance.

Genus	Virus	Comments
Morbillivirus	Rinderpest virus	Cause of cattle plague, a highly contagious disease in domestic and wild ruminants, characterized by high morbidity and high mortality. Worldwide eradication announced by FAO in 2011
	Peste des petits ruminants virus	Produces severe disease, resembling rinderpest, in small ruminants, particularly sheep and goats, with high morbidity and high mortality rates
	Canine distemper virus	Acute disease in dogs and wild carnivores, characterized by multi-systemic involvement, including CNS signs, and variable mortality
Avulavirus	Newcastle disease virus (Avian paramyxovirus 1)	Generalized infection characterized by respiratory, intestinal and nervous signs in domestic and wild birds. Isolates vary widely in virulence; velogenic, mesogenic and lentogenic strains are recognized
	Avian paramyxovirus 2–9	Reported worldwide from a range of domestic and wild birds. Although infections with most avian paramyxoviruses are associated with mild or inapparent disease, infections with APMV-2 and APMV-3 have been associated with respiratory disease in turkeys
Rubulavirus	Porcine rubulavirus	Known as blue eye disease, characterized by mortality in young pigs, corneal opacity and reproductive failure; described only in Mexico
	Canine parainfluenza virus	Causes inapparent or mild respiratory disease in dogs; sometimes associated with kennel cough; also known as parainfluenza virus 5 (formerly simian virus 5)
Respirovirus	Bovine parainfluenza virus 3	Cause of subclinical or mild respiratory disease in cattle and sheep. Sometimes associated with shipping fever in cattle. Predisposes to secondary bacterial infection, particularly with Mannheimia haemolytica
Pneumovirus	Bovine respiratory syncytial virus	Common subclinical infection in adult cattle. Associated with respiratory disease outbreaks of varying severity in young cattle. Sheep and goats are also susceptible
Metapneumovirus	Avian metapneumovirus	Causes severe upper respiratory tract infection in turkeys, with coryza and swollen sinuses. In chickens, the disease is referred to as ‘swollen head syndrome’

Rinderpest

This acute OIE-listed disease, which occurred primarily in ruminants and is also referred to as cattle plague, has been recognized for centuries as a major cause of mortality in cattle and domestic buffalo. Originally an Asian disease, devastating outbreaks in Europe resulted in the foundation of the first veterinary school in Lyon in 1761. Following its introduction into the Horn of Africa a devastating outbreak followed throughout sub-Saharan Africa during the last decade of the nineteenth century. Due to the labile nature of the virus, transmission, which occurs through aerosols, usually requires close contact. Epidemics usually occur following movement of susceptible animals into an endemic area or the introduction of infected animals into susceptible populations. Infected animals develop fever and become anorexic and depressed. Mucosal erosions in the mouth and nasal passages become evident within five days. Profuse salivation is accompanied by an oculonasal discharge. About three days after the appearance of the mucosal ulcers, fever regresses and a profuse diarrhoea develops. The dark fluid faeces often contain mucus, necrotic debris and blood. Morbidity may reach 90% and mortality can approach 100%. Following various regional initiatives, the Food and Agriculture Organization (FAO) launched a global eradication scheme in 1994 that involved movement restrictions, vaccination, active surveillance and culling. By the end of the twentieth century rinderpest was considered endemic only in the Somali pastoral ecosystem which straddles the borders of Kenya, Ethiopia and Somalia. However, the virus had not been confirmed in this area since 2001. The FAO announced the worldwide eradication of rinderpest in 2011, making it the first animal virus and, after smallpox virus, only the second virus to be eradicated.

Peste des petits ruminants

This condition, also referred to as goat plague, is an acute contagious disease of small ruminants, particularly goats. It is an OIE-listed disease and occurs in sub-Saharan Africa north of the equator, the Middle East, India and Pakistan. Close contact is required for transmission of this labile virus which occurs through aerosols. The introduction of infection into a flock is invariably associated with movement of animals. Infection rates are similar in sheep and goats but the disease is generally more severe in goats. The disease is particularly severe in young animals with affected animals exhibiting fever, dry muzzle and a serous nasal discharge which becomes mucopurulent. Erosions in the buccal cavity are accompanied by marked salivation. Ulcers develop in the mucosae of the alimentary, respiratory and urinary tracts. Conjunctivitis with ocular discharge is a feature of the disease. A profuse diarrhoea, which results in dehydration, develops within days of infection. Signs of tracheitis and pneumonia are common. Pulmonary infections caused by Pasteurella species are common in the later stages of the disease. Pregnant animals may abort. Mortality rates in severe outbreaks often exceed 70%.

Laboratory confirmation is based primarily on RT-PCR. Antibodies can be detected by virus neutralization or by competitive ELISA. In regions where the disease is endemic, quarantine and vaccination are used for control.

Canine distemper

This highly contagious disease of dogs and other carnivores has a worldwide distribution. Outbreaks of disease have been documented in several wildlife species including lions. Canine distemper virus (CDV), a pantropic morbillivirus, produces a generalized infection involving many organ systems including the skin, respiratory, gastrointestinal, urinary and central nervous systems. The virus is relatively labile, requiring transmission by direct contact or by aerosols. Infection spreads rapidly among young dogs, usually between three and six months of age, when maternally derived immunity declines. The severity and duration of illness are variable and are influenced by the virulence of the infecting virus, the age and immune status of the infected animal and the rapidity of the immune response to infection. Acute disease, which may last for a few weeks, is followed either by recovery and lifelong immunity or by the development of neurological signs and, eventually, death. Modified live vaccines provide good protection when administered to pups after maternally derived antibody has declined to low levels, usually after 12 weeks of age. Clinical cases are comparatively rare in countries where vaccination is widely practised.

Old dog encephalitis, characterized by motor and behavioural deterioration many years after recovery from CDV infection, is invariably fatal. It is probably associated with non-cytolytic spread of virus from cell to cell, thereby evading immune detection.

Newcastle disease

Virulent strains of Newcastle disease virus (NDV), also known as avian paramyxovirus serotype 1 (APMV-1), cause disease in poultry worldwide. A wide range of avian species including chickens, turkeys, pigeons, pheasants, ducks and geese are susceptible. A reservoir of NDV exists in wild birds, especially pigeons and waterfowl.

Strains of NDV differ in their virulence and isolates are categorized into five pathotypes on the basis of virulence and tissue tropism in poultry:

• viscerotropic velogenic isolates causing severe fatal disease characterized by haemorrhagic intestinal lesions (Doyle's form);
• neurotropic velogenic isolates causing acute disease characterized by nervous and respiratory signs with high mortality (Beach's form);
• mesogenic isolates causing mild disease with mortality confined to young birds (Beaudette's form);
• lentogenic isolates causing mild or inapparent respiratory infection (Hitchner's form);
• asymptomatic enteric isolates associated with subclinical intestinal infection.

The extent of spread within the body relates to strain virulence which is determined by the amino acid sequence of the F glycoprotein. The fusion (F) glycoprotein of NDV is synthesized in an infected cell as a precursor molecule (F₀) which is cleaved by host cell proteases to F₁ and F₂ subunits. If cleavage fails to occur, non-infectious particles are produced. The F₀ molecules of virulent strains of NDV possess multiple basic amino acids at critical positions which facilitate intracellular cleavage by proteases such as furin, present in a wide range of host tissues. In contrast, the replication of lentogenic strains is confined to the respiratory and intestinal epithelia where suitable trypsin-like proteases are produced.

Virus is shed in all excretions and secretions. Transmission usually occurs by aerosols or by ingestion of contaminated feed or water. Respiratory, gastrointestinal and nervous signs occur in chickens. The mortality rate in fully susceptible flocks may be close to 100%. A presumptive clinical diagnosis may be made when the characteristic signs and lesions associated with virulent strains are present. Laboratory confirmation by isolation and identification of the virus is necessary. Molecular techniques are increasingly being used for the detection of NDV in clinical specimens. Primers are usually selected to cover the cleavage site of the F₀ protein gene, thus providing information on the virulence of the virus detected. The current OIE definition for reporting an outbreak of Newcastle disease is infection of birds by avian paramyxovirus serotype 1 with either an intracerebral pathogenicity index (ICPI) ≥0.7 in day-old chicks or with multiple (at least three) basic amino acids at the C-terminus of the F₂ protein and phenylalanine at residue 117 (N-terminus of the F₁ protein). A combination of vaccination and slaughter is frequently employed to control disease outbreaks. Vaccination is particularly important for birds in breeder flocks. Lentogenic or mesogenic strains of NDV propagated in eggs or tissue culture are used in live vaccines.

Pigeons are susceptible to all strains of NDV and may play a role in the transmission of Newcastle disease. Isolates from pigeons, often referred to as ‘pigeon’ paramyxovirus 1 (PPMV-1), are associated with clinical disease in racing pigeons resembling the neurotropic form of Newcastle disease. Many PPMV-1 viruses are also pathogenic for commercial poultry.

Bovine parainfluenza virus 3

Infection with bovine parainfluenza virus 3 (BPIV-3), which occurs worldwide, is often subclinical. Clinical disease is most common in calves with low levels of maternal antibodies. Transmission, which occurs by aerosols and direct contact, is facilitated by overcrowding in poorly ventilated conditions. Although uncomplicated infections are frequently subclinical, mild respiratory disease may be seen. The virus is commonly isolated from animals during outbreaks of serious respiratory disease such as enzootic calf pneumonia and shipping fever, conditions in which other respiratory viruses and bacteria are often involved. Various stress factors such as transportation or adverse environmental conditions may contribute to the severity of the disease.

Both inactivated and modified live BPIV-3 vaccines are available, often combined with other respiratory viruses. Modified live vaccines are designed either for intranasal administration or for intramuscular injection. Immunity tends to be short-lived and reinfection may occur after some months.

Bovine respiratory syncytial virus

Pulmonary disease, caused by bovine respiratory syncytial virus (BRSV), occurs in beef and dairy calves worldwide. The virus replicates mainly in ciliated epithelial cells of the upper respiratory tract. The virus derives its name from the characteristic syncytia which it induces in infected cells. Infection with BRSV stimulates production of proinflammatory cytokines and an excessive inflammatory reaction that results in respiratory disease. In adult animals, infection is usually mild or subclinical with persistent infection considered to be responsible for the maintenance of infection in herds. Moderate to severe respiratory signs typically develop in animals between three and nine months of age. Clinical signs, which range from mild to severe, include fever, nasal and lacrimal discharge, coughing and polypnoea. A biphasic pattern is commonly observed in outbreaks among beef calves. Mild respiratory disease is followed by apparent recovery and, within a few days, dyspnoea and pulmonary emphysema develop. Mortality in these outbreaks may reach 20%.

Clinical signs and pathological findings may permit a presumptive diagnosis. Laboratory confirmation by viral antigen detection, RT-PCR or serological testing is necessary for a definitive diagnosis. Suitable control measures include reducing stress factors, maintaining good hygiene in calf pens, rearing calves away from older age groups and implementing a closed herd policy. Modified live vaccines may be administered parenterally or intranasally. Although vaccination tends to reduce the likelihood of clinical disease in exposed animals, the duration of protection is short and frequent boosters may be required.