1. Paramyxoviiruses September 21,22, 2010

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

3. 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 respiratory syncytial virus canine distemper Newcastle disease virus Hendra Nipah Henipah

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

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

6. Receptor binding and penetration GenusReceptor attachment Main Penetration or Fusion protein Paramyxovirus (PI3) HNF (cleaved by cellular proteases) Pneumovirus (BRSV) G (no neuraminidase)F (cleaved by cellular proteases) Morbillivirus (CDV) H (no neuraminidase)F (cleaved by cellular proteases)

7. Syncytium ( pl. syncytia ) formation activated fusion protein budding virus uninfected cells 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. Morbilliviruses Rinderpest Pestes des petit ruminants Canine distemper virus Morbilliviruses of marine mammals Measles Hendra virus (equine morbillivirus) Nipah virus

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 recoverydeath acute neurological signs recoverydeath chronic neurological signs death“old dog encephalitis”

15. 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

16. Chronic disease With immunological recovery - inflammation in demyelinating lesions - progressive 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. Diagnosis of distemper clinical signs Laboratory –PCR –Serology Serum + CSF (NO EDTA) Paired samples –Immunohistochemistry

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

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

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

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

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

28. 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

29. 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

30. 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

31. 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

32. Possible causes Avocado poisoning Brown snake bite

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

34. 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

35. 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

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

37. 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.

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

39. 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?)

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

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

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

43. Nipah human to human transmission