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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. influenzaviruses. Orthomyxoviridae. parainfluenza virus. Paramyxoviruses. Newcastle disease virus. respiratory syncytial virus.

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Paramyxoviiruses


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paramyxoviiruses

Paramyxoviiruses

September 21,22, 2010

viruses with ve rna genomes
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

paramyxoviruses
Enveloped

Genome - single negative stranded RNA molecule

Helical nucleocapsid with herring-bone appearance

Paramyxoviruses
a paramyxo virion
A paramyxo virion

HN (paramyxo)

H (morbilli)

G(pneumo)

“herring-bone”

nucleocapsid

Fusion

Protein (F)

(syncytia when

on cell)

syncytium pl syncytia formation
Syncytium (pl. syncytia) formation

uninfected

cells

activated

fusion protein

budding

virus

syncytium

syncytia
Syncytia

syncytia

importance of type of immunity
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
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

Morbilliviruses
canine distemper 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
pathogenesis
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

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

Acute neurological disease
long term persistence in cns
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
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

Diagnosis of distemper
prevention of distemper
Inactivated vaccines

Modified live

USE ONLY IN DOMESTIC DOGS!

Vectored vaccine (Recombitek, Merial)

Heterotypic vaccine (measles)

Prevention of distemper
a case of distemper in saskatoon
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

Other morbilliviruses
rinderpest
Wild and domestic ruminants, pigs

Direct contact or contaminated water

High fever

Purulent discharge

Erosion of oral mucosa

Bloody diarrhoea

Rinderpest
a new disease in horses and people 1994
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

At a stable in Hendra (1994)
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
diagnostic investigation30
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
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

At a farm near MacKay (July 1994)
mackay august 1994
Husband becomes sick

Sore throat, headaches, etc.

CSF - neutrophilia, no virus or bacteria identified

Responds to antibiotics - recovers

MacKay August 1994
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

MacKay September 1995
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

Equine morbillivirus
nipah 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.

Nipah disease
porcine respiratory encephalitis syndrome barking pig syndrome
Fever

Coughing

Respiratory distress

Trembling, head pressing, spasms

Abortions, still births

Porcine respiratory encephalitis syndrome, barking pig syndrome
nipah virus39
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
slide40
Why?

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

control
Control

1 million pigs killed

reduce pig-human contact