Paramyxoviridae Family: Viral Classification

Paramyxoviridae Family

• Viruses in the Paramyxoviridae family are called Paramyxoviruses.
• They belong to the order Mononegavirales that encompasses virus families such as Rhabdoviridae, Filoviridae, and Bornaviridae.
• Several devastating diseases of animals, birds, and humans are caused by Paramyxoviruses, including rinderpest, canine distemper, Newcastle disease, Nipah, measles, and mumps.
• The impact has been reduced through vaccination.
• Of concern are paramyxoviruses in the Henipavirus genus whose natural host is the fruit bat but are highly infectious for swine, and humans.

Classification of Paramyxoviruses

• Family: Paramyxoviridae
• Subfamilies can include: Avulavirinae, Metaparamyxovirinae, Orthoparamyxovirinae, and Rubulavirinae.
• Orthoavulavirus has a species called Avian orthoavulavirus 1 known as Newcastle disease.
• Nipah virus is in the Henipavirus genus.
• Canine distemper virus is within the Morbillivirus genus.
• Bovine respiratory syncytial virus is in the Respirovirus genus.

Virion Properties

• Virions are pleomorphic, either spherical or filamentous, and range from 150-350 nm in diameter.
• They are enveloped with large glycoprotein spikes measuring around 8-14 nm.
• Virions contain a "herringbone-shaped" nucleocapsid.
• The genome consists of linear, single-stranded, negative-sense RNA, ranging from 13-19 kb in size.

Virion Structure

• Lipid bilayer
• Three membrane proteins: Fusion protein (F), attachment protein hemagglutinin (H), and unglycosylated matrix protein (M).
• Three nucleocapsid proteins (RNP): include RNA-binding protein (N), phosphoprotein (P), and large polymerase (L).
• Attachment Proteins: Hemagglutinin-neuraminidase (HN) OR glycoprotein (G).
• Envelope spikes: Composed of 2 glycoproteins, F, and G or F and HN or F and H.
• Spike glycoproteins play an important role in the pathogenesis of paramyxovirus.
• Glycoprotein (HN, H, or G) is responsible for attachment, and the F protein mediates fusion of the viral envelope with the cell membrane.
• Antibodies directed against these proteins are neutralizing antibodies.

Replication

• Replication of paramyxoviruses leads to lysis of infected cells or formation of syncytium.
• Paramyxoviruses produce cytoplasmic acidophilic inclusion bodies, composed of ribonucleoprotein structures.
• Morbiliviruses produce acidophilic intranuclear inclusion bodies composed of nuclear elements and protein N.
• Hemoadsorption and hemagglutination are distinctive features of paramyxoviruses that express the H or HN protein.

Newcastle Disease

• Newcastle disease (ND) virus, is caused by virulent strains of avian paramyxovirus type 1 (APMV-1).
• The virus is a member of the Paramyxoviridae family in the subfamily Avulavirinae, genus Orthoavulavirus.
• It is also known as Avian orthoavulavirus 1.
• Five pathotypes include: viscerotropic velogenic, neurotropic velogenic, mesogenic, lentogenic or respiratory, and asymptomatic.
• Chickens are highly susceptible to this disease, while turkeys typically do not develop severe signs.
• Wild birds and waterfowl (order Anseriformes) may harbor the virus subclinically.
• Also recorded in ostriches and penguins (order Sphenisciformes)
• Morbidity and mortality rates vary with the pathotype of infecting virus and species.
• Humans may become infected, which is manifested by unilateral or bilateral reddening of eyes, excessive lacrimation, oedema of the eyelids, conjunctivitis, and sub-conjunctival haemorrhage.
• Direct contact facilitates transmission with secretion of infected birds via ingestion (faecal/oral route) and inhalation.
• Fomites, include feed, water, premises, human clothing, boots, sacks, and egg trays/crates, can spread the virus.
• Hatching chicks may be infected through the egg for some NDV strains.
• Incubation period ranges from 2-15 days, with an average of 5-6 days, and may exceed 20 days in some bird species.
• Velogenic NDV is endemic in areas of Mexico, Central and South America, widely spread in Asia, the Middle East and Africa, and in double-crested wild cormorants in the US and Canada.
• Lentogenic strains of NDV are worldwide in their distribution.
• Clinical signs of NDV vary because they depend on factors such as the virus/pathotype, host species, age of host, co-infection with other organisms, environmental stress and immune status.
• Clinical signs do not provide a reliable basis for diagnosis of ND.

Lentogenic Strains

• Lentogenic strains are usually associated with a subclinical disease.
• These include mild respiratory symptoms like coughing, gasping, and sneezing with rales.
• Lentogenic strains can cause severe signs if co-infectious agents are present.
• The mortality of Lentogenic strains is negligible.

Mesogenic Strains

• Mesogenic strains may cause acute respiratory disease with neurologic signs in some species.
• Mortality rate is usually low, around than 10%.
• If co-infection occurs with other agents, disease can results in severe signs.

Velogenic Strains

• Velogenic strains cause severe disease in chickens and lead to high mortality.
• Velogenic strains often result in sudden death, with few or no signs.
• Specific signs include respiratory and/or nervous problems, and affect the digestive tract.
• Initial clinical signs vary and can include lethargy, inappetence, ruffled feathers, and oedema.
• Later, greenish or white watery diarrhoea, dyspnoea and inflammation of the head and neck can occur, often with cyanotic discoloration.
• Neurologic signs are: tremors, tonic/clonic spasms, wing/leg paresis or paralysis, torticollis, and aberrant circling behaviour.
• Sharp egg production drop may occur. Eggs contain a watery albumin and abnormally colored, rough, or thin shells.
• Morbidity and mortality rates may approach 100% in unvaccinated chickens.
• Birds that survive serious infection may develop neurologic disease and partial or complete cessation of egg production.

Lesions

• No pathognomonic gross lesions.
• Several birds must be examined to determine a tentative diagnosis.
• Diagnosis awaits virus detection and identification.
• Velogenic strains specifically may produce swelling of periorbital area or entire head as significant gross lesions.
• Other indicators: oedema of the interstitial, peritracheal tissue of the neck, or oedema, haemorrhages/degeneration of ovaries.
• Look for oedema, haemorrhages, necrosis or ulcerations of respiratory/digestive tract and lymphoid tissue.

Laboratory Diagnosis

• Collect samples from recently dead or moribund birds.
• Samples should be sent to a reference laboratory.
• Collect oro-nasal swabs; lung, kidneys, intestine (including contents), cecal tonsils, spleen, brain, liver and heart tissues, separately or as a pool from dead birds.
• Tracheal or oropharyngeal and cloacal swabs are collected from live birds.
• Collect clotted blood samples or blood for serum, and perform serology.
• Perform inoculation of embryonated specific pathogen free (SPF) eggs and testing for haemagglutination (HA) activity.
• An Enzyme-linked immunosorbent assay (ELISA) tests for screening in un-vaccinated flocks.
• There are also validated specific molecular methods such as PCR.

Differential Diagnosis

• A differential diagnosis should consider: fowl cholera, highly pathogenic avian influenza, laryngotracheitis, fowl pox (diphtheritic form), psittacosis (psittacine birds), mycoplasmosis, infectious bronchitis, and aspergillosis.

Prevention and Control

• Vaccination with live vaccines is a key preventative measure.
• 2 conventional live virus vaccines include: lentogenic and mesogenic vaccines.
• Live virus vaccines are administered by incorporation in drinking water, application as a coarse spray (aerosol) or intranasally/conjunctival instillation.
• More expensive Inactivated vaccines.
• New recombinant vaccines such as fowlpox, vaccinia, pigeonpox, turkey herpesvirus and avian cells in which the HN are inserted .
• Preventative methods: Bird-proofing houses/feed/water supplies, proper carcass disposal or pest control and ("all in-all out") breeding methods.

Nipah Virus

• Named after the village of "Sungai Nipah" in Malaysia.
• It is an emerging zoonosis that causes severe disease in animals and humans.
• Causes encephalitis and respiratory illness.
• Barking Pig Syndrome, Porcine Respiratory and Encephalitis Syndrome, and Porcine Respiratory and Neurologic Syndrome, are synonyms for Nipah in pigs.
• It is a notifiable disease.
• In the Henipavirus genus, the Nipah virus was discovered in 1999, and related to Hendra virus.
• Nipah causes severe, rapidly progressive encephalitis in humans.
• Transmission: flying foxes (fruit bats), urine, saliva.
• No known secondary host.
• Incubation period in pigs is approximately 7-14 days and approximately 4 to 20 days in humans.
• Clinical signs in pigs: Laboured breathing and muscle tremors with limb weakness in suckling piglets.
• Transmitted by close contact with infected pigs.
• The disease is a biosafety level 4 agent, calling for special precautions during sample collection, submission and processing.
• real-time PCR recognition methods.
• Sanitation biosecurity measures of swine.

Canine Distemper Virus

• Belongs to the Morbilivirus genus.
• This virus is a highly contagious, acute febrile disease of dogs.
• It is a rare disease in dogs in the developed world.
• The lineages of canine distemper virus include Asia, America, and Europe.
• Canine distemper is identified in raccoons the USA.
• Clinical diseases include mild, and severe generalized distemper.
• Fever with respiratory tract infections such as coughing.
• The virus is shed in all secretions and excretions from the 5th day after infection.
• Transmitted mainly through direct contact, droplets, and aerosols.
• Initially replicates in the upper respiratory tract macrophages followed by the blood
• It then infects t and B cells which leads to primary viremia.