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Paramyxoviiruses

September 21,22, 2010

rinderpest and the beginning of modern veterinary medicine

Giovanni Maria Lancisi

Viruses with -ve RNA genomes


Orthomyxoviridae
influenzaviruses

Paramyxoviruses Paramyxoviridae
Rhabdoviridae
rabies virus Ebola virus

parainfluenza virus
Newcastle disease virus

Pneumoviruses

respiratory syncytial virus

Morbilliviruses
Henipah
vesicular stomatitis virus

canine distemper Hendra Nipah

Filoviridae Bunyaviridae

Haantan virus

Paramyxoviruses
Enveloped Genome - single negative stranded RNA molecule Helical nucleocapsid with herring-bone appearance

A paramyxo virion
HN (paramyxo) H (morbilli) G(pneumo)
herring-bone nucleocapsid

Fusion Protein (F) (syncytia when on cell)

Receptor binding and penetration


Genus Receptor attachment
HN

Main Penetration or Fusion protein


F (cleaved by cellular proteases) F (cleaved by cellular proteases) F (cleaved by cellular proteases)

Paramyxovirus (PI3) Pneumovirus (BRSV) Morbillivirus (CDV)

G (no neuraminidase)

H (no neuraminidase)

Syncytium (pl. syncytia) formation


uninfected cells activated fusion protein

budding virus

syncytium

Syncytia
syncytia

Eosinophilic cytoplasmic inclusion bodies

Importance of type of immunity


neutralizing and fusion preventing antibodies are protective non-neutralizing antibodies can exacerbate disease (children vaccinated with formalin inactivated vaccine) Th1 better than Th2 CMI

Respiratory disease by Paramyxo and Pneumoviruses


bovine
parainfluenzavirus 3 (PI3) respiratory syncytial virus (BRSV)

dogs
PI2

birds
Newcastle disease virus (clinical features depend on strain)

Morbilliviruses
Rinderpest Pestes des petit ruminants Canine distemper virus Morbilliviruses of marine mammals Measles Hendra virus (equine morbillivirus) Nipah virus

canine distemper virus


complex disease - enteric, respiratory, lymphoid, neural effects wide range of carnivore species
Canidae (main reservoir) Procyonidae (raccoons) Mustelidae (ferrets, mink) Ailuronidae (pandas) Felidae (Panthera not domestic cats)

marine mammals

infection

Pathogenesis
asymptomatic incubation period (7-10 days)

GI and respiratory signs, infection of epithelial cells

recovery

death

acute neurological signs

recovery

death

chronic neurological signs death

old dog encephalitis

Acute neurological disease


Virus replicates in neurons and glial cells Demyelination in white matter in absence of inflammation No virus replication in oligodendroglial cells but suppression of myelin synthesis Immunological recovery - Lymphocytic infiltration, intrathecal antibody synthesis

Chronic disease
With immunological recovery inflammation in demyelinating lesions progressive disease

Long-term persistence in CNS


Non-cytolytic replication Cell to cell spread without budding - no antigens on surface Virus reactivation or immune-mediated damage

Clinical signs
asymptomatic (most dogs) partial immunity general fever, depression, anorexia, discharge from eyes/nose, enteric vomiting, diarrhoea respiratory coughing, sneezing, dyspnea neural weakness, ataxia, incoordination, epileptic seizures, myoclonus, chewing gum fits other hyperkeratosis of nose and foot pads old dog encephalitis visual defects, compulsive circling, head pressing

Diagnosis of distemper
clinical signs Laboratory
PCR Serology
Serum + CSF (NO EDTA) Paired samples

Immunohistochemistry

Ante-mortem diagnosis by immunohistochemistry (Haines and Clark, WCVM)

Prevention of distemper
Inactivated vaccines Modified live
USE ONLY IN DOMESTIC DOGS!

Vectored vaccine (Recombitek, Merial) Heterotypic vaccine (measles)

A case of distemper in Saskatoon


In December a 4-5 month old American Pitbull cross was brought to a Saskatoon animal shelter as a stray. The puppy was vaccinated with DA2PCPV and was adopted out on December 23. The puppy was returned to the shelter on December 29 as he was coughing. On January 3, the attendant described the pup as acting weird - head pressing, stumbling and twitching were observed. Within the next week several dogs at the shelter developed respiratory signs. For the next several days about 10 dogs a day were brought to the WCVM clinic with signs of distemper. All dogs at the shelter were euthanised and it was closed for traffic.

Other morbilliviruses
Horse morbillivirus (Hendra virus) Nipah virus Rinderpest Pestes des petit ruminantes

Rinderpest
Wild and domestic ruminants, pigs Direct contact or contaminated water High fever Purulent discharge Erosion of oral mucosa Bloody diarrhoea

A new disease in horses and people (1994)


Cairns Townsville MacKay

Queensland
Brisbane (Hendra)

At a stable in Hendra (1994)


Two horses moved to stable Drama Series becomes sick and dies Within three weeks 13 horses die
Respiratory, CNS, haemorrhages in lung

Stable hand and trainer become sick Trainer dies

Diagnostic investigation
Rule out AHS, flu, EHV-1, bacteria, toxins See syncytia in cultures - suspect paramyxovirus PCR for PI and pneumoviruses is negative PCR for morbillivirus +ve Sequence -> new virus Cross reactivity between human and horse sera

Diagnostic investigation
More than 3,000 serum samples, horses and people negative 5,000 samples from 46 species - negative Antibodies in fruit bats Virus isolated

At a farm near MacKay (July 1994)


Pregnant mare at pasture develops respiratory signs Moved to paddock Mare develops respiratory distress, ataxia, edema ->dies Stallion in next paddock, neuro. Signs, haemorrhages ->dies Owner (vet) and husband perform necropsy

Possible causes

Avocado poisoning Brown snake bite

MacKay August 1994


Husband becomes sick
Sore throat, headaches, etc. CSF - neutrophilia, no virus or bacteria identified Responds to antibiotics - recovers

MacKay September 1995


Husband readmitted
Neuro signs, seizures Treated with acyclovir, antibiotics, anticonvulsants, corticosteroids Coma - dies three weeks later

Diagnostic
CSF from 1994 - 1/4 for EMV, virus by PCR In 1995, increase in titre from 1/16 to 1/5792 Necrosis in neocortex, basal brain, brain stem, cerebellum

Equine morbillivirus
Horses, people, cats, guinea pigs infected Fruit bats can be infected but no disease Excreted in feces, urine, infection by eating shed virus

Nipah Virus
Oct 98 to April 99 - 257 cases of encephalitis (100 deaths) Similar disease in pigs

Nipah disease
Fever, severe head aches, muscle pain Common - association with pigs Initially thought to be Japanese encephalitis Syncytia, paramyxovirus on EM Virus isolated, Univ. Malaya and CDC Similar to Hendra virus Serological confirmation that virus involved in outbreak.

Porcine respiratory encephalitis syndrome, barking pig syndrome


Fever Coughing Respiratory distress Trembling, head pressing, spasms Abortions, still births

Nipah virus
Pigs, humans, dogs, cats, rats and horses can be infected Serological evidence in fruit bats (reservoir?) virus from fruit bats - 2002 2004-5 - human cases in Bangladesh (no contact with pigs or bats, contaminated fruit?)

Why?

Chou. Nipah virus outbreak in Malaysia. J Clin Virol April 2003

Control
1 million pigs killed reduce pig-human contact

Nipah in Balgladesh Possible contamination of date-palm sap by Nipah virus

Nipah human to human transmission

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