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Paramyxoviiruses

Paramyxoviiruses. September 21,22, 2010. rinderpest and the beginning of modern veterinary medicine. Giovanni Maria Lancisi. Viruses with -ve RNA genomes. influenzaviruses. Orthomyxoviridae. parainfluenza virus. Paramyxoviruses. Newcastle disease virus. respiratory syncytial virus.

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Paramyxoviiruses

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  1. Paramyxoviiruses September 21,22, 2010

  2. rinderpest and the beginning of modern veterinary medicine Giovanni Maria Lancisi

  3. Viruses with -ve RNA genomes influenzaviruses Orthomyxoviridae parainfluenza virus Paramyxoviruses Newcastle disease virus respiratory syncytial virus Pneumoviruses Paramyxoviridae Morbilliviruses canine distemper Henipah Rhabdoviridae Hendra Nipah vesicular stomatitis virus rabies virus Filoviridae Ebola virus Bunyaviridae Haantan virus

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

  5. A paramyxo virion HN (paramyxo) H (morbilli) G(pneumo) “herring-bone” nucleocapsid Fusion Protein (F) (syncytia when on cell)

  6. Receptor binding and penetration

  7. Syncytium (pl. syncytia) formation uninfected cells activated fusion protein budding virus syncytium

  8. Syncytia syncytia

  9. Eosinophilic cytoplasmic inclusion bodies

  10. 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

  11. 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)

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

  13. 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

  14. Pathogenesis infection asymptomatic incubation period (7-10 days) GI and respiratory signs, infection of epithelial cells recovery death acute neurological signs recovery death chronic neurological signs “old dog encephalitis” death

  15. 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 Acute neurological disease

  16. With immunological recovery - inflammation in demyelinating lesions - progressive disease Chronic disease

  17. Long-term persistence in CNS • Non-cytolytic replication • Cell to cell spread without budding - no antigens on surface • Virus reactivation or immune-mediated damage

  18. 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

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

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

  21. Inactivated vaccines Modified live USE ONLY IN DOMESTIC DOGS! Vectored vaccine (Recombitek, Merial) Heterotypic vaccine (measles) Prevention of distemper

  22. 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.

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

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

  25. A new disease in horses and people (1994) Cairns Townsville MacKay Queensland Brisbane (Hendra)

  26. 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 At a stable in Hendra (1994)

  27. 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

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

  29. 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 At a farm near MacKay (July 1994)

  30. Avocado poisoning Brown snake bite Possible causes

  31. Husband becomes sick Sore throat, headaches, etc. CSF - neutrophilia, no virus or bacteria identified Responds to antibiotics - recovers MacKay August 1994

  32. 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 MacKay September 1995

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

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

  35. 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. Nipah disease

  36. Fever Coughing Respiratory distress Trembling, head pressing, spasms Abortions, still births Porcine respiratory encephalitis syndrome, barking pig syndrome

  37. 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?) Nipah virus

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

  39. Control 1 million pigs killed reduce pig-human contact

  40. Nipah in BalgladeshPossible contamination of date-palm sap by Nipah virus

  41. Nipah human to human transmission

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