Paramyxoviiruses

September 21,22, 2010

rinderpest and the beginning of modern veterinary medicine

Giovanni Maria Lancisi

Viruses with -ve RNA genomes

Paramyxoviridae

Rhabdoviridae

Orthomyxoviridae

Filoviridae

Bunyaviridae

rabies virus

vesicular stomatitis virus

influenzaviruses

Ebola virus

Haantan virus

Paramyxoviruses

Pneumoviruses

Morbilliviruses

parainfluenza virus

respiratorysyncytial virus

canine distemper

Newcastle disease virus

HendraNipah

Henipah

Paramyxoviruses

• Enveloped

• Genome - single negative stranded RNA molecule

• Helical nucleocapsid with herring-bone appearance

A paramyxo virion

FusionProtein (F)(syncytia whenon cell)

“herring-bone”nucleocapsid

HN (paramyxo)H (morbilli)G(pneumo)

Receptor binding and penetration

Genus Receptor attachment

Main Penetration or Fusion protein

Paramyxovirus

(PI3)

HN F (cleaved by cellular proteases)

Pneumovirus

(BRSV)

G (no neuraminidase) F (cleaved by cellular proteases)

Morbillivirus

(CDV)

H (no neuraminidase) F (cleaved by cellular proteases)

Syncytium (pl. syncytia) formation

activatedfusion protein

buddingvirus

uninfectedcells

syncytium

Syncytiasyncytia

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

Pathogenesisinfection

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 replicationCell 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)

MacKay

Brisbane

Queensland

(Hendra)

CairnsTownsville

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 VirusOct ‘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 BalgladeshPossible contamination of date-palm sap by

Nipah virus

Nipah human to human transmission