Paramyxoviridae Siamak Zohari Avdelning för Virologi, Immunbiologi och Parasitologi, Statens Veterinärmedicinska Anstalt, SVA

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Paramyxoviridae

Siamak Zohari

Avdelning för Virologi, Immunbiologi och Parasitologi, Statens Veterinärmedicinska Anstalt, SVA Siamak.Zohari@sva.se

Paramixoviridae Paramyxovirinae

Pneumovirinae

Aquaparamyxovirus Avulavirus Henipavirus

Morbillivirus Respirovirus

Rubula virus

Metapneumovirus

Pneumovirus

Avian metapneumovirus Human metapneumovirus

Bovine respiratory syncytial virus Human respiratory syncytial virus Murine pneumonia virus Canine parainfluenza virus 2 Human parainfluenza virus 4 Mapuera virus Mumps virus Parainfluenza virus 5 Porcine rubulavirus Simian virus 41 Rinderpest Pest des Petit Ruminants Canine Distemper virus Cetacean Morbillivirus Mealses virus Phocine distemper virus Hendra Nipha

Bovineparainfluenza virus 3 Human parainfluenza virus 1 Human parainfluenza virus 3 Sendai virus Atlantic Salmon Paramyxovirus

Avian Paramyxovirus 1-11 (NDV=aPMV1)

Ordningen; Mononegavirales Ferlavirus Fer-de-Lance paramyxovirus

Enkelt strängad RNA virus Med negativ polaritet

Ordningen; Mononegavirales

Paramyxovirion

Fusionsprotein (F) “fiskbens-

liknande”

nukleokapsid Avulavirus, HN

Respirovirus HN Rubulavirus, HN Morbilli, H Pneumo, G

Attachmentprotein

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2

N P

Leaky Scanning

C’ C Y1 Y2

V

W mRNA editing

M F H

3’ L

leader Trailer

5’

Paramyxovirinae

Aquaparamyxovirus Atlantic Salmon Paramyxovirus 16964 nt Ferlavirus Fer-de-Lance paramyxovirus 15378 nt

Rubulavirus Simian virus 5 15246 nt

Avulavirus Newcastle disease virus 15156 nt

Respirovirus Sendai virus 15384 nt

Henipavirus Hendra virus 18234 nt

Morbillivirus Measles virus 15894 nt

Pneumovirinae

Pneumovirus- Human respiratory syncytial virus- 15222 nt Metapneumovirus- Human metapneumovirus- 13350 nt

Pneumovirus

1 2 N P M SH G F M2 L

NS

Metapneumovirus M2

N P M F SH G L

3’ 5’

Ferlavirus

N U P M F HN L

3’ 5’

Rubulavirus

N P M F SH HN L

3’ 5’

Receptor binding and Entry

Release Packaging and Budding

IFN

Endocytosis

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Canine distemper virus (H) Newcastle disease virus (HN) Bovine respiratory syncytial virus (G) Hendra virus (G)

Nipah virus (G)

SLAM (signaling lymphocyte activation molecule)

Sialic acid Unknown Ephrin-B2 Ephrin-B2

Exempel på cellulära makromolekyler som används av virus som receptorer

Fusion protein

Fusion gene plays an important role Post translation cleavage required for infectivity

Presence of multiple basic amino acids at the cleavage site of the fusion (F) protein Presence of arginine at positions 113 and 116,

and arginine/lysine at 115 Phenylalanine at 117

GG112-RRRKR-116FI GG112-KQGRL-116LI

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4

CPE: Measles on human lung carcinoma (A549)

Syncytia

• P=ORF begin at nucleotide 1807

• V=ORF begin at nucleotide 1807 but polymerase slipping at editing site (nt 2487-2498), frameshift and insertion of G in mRNA to C- terminus

• C=ORF begin at nucleotide 1829

V

C

299 aa

178 aa RNA editing at nt position

2487 2498

N P M F H

3’ L

Leader Trailer

5’

P

P 510 aa

-SS RNA// PPRV genome

-P gene

-P protein

-V protein

-C protein Leaky Scanning

mRNA editing

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Rinderpest, RPV

Paramyxovirinae Morbillivirus Mononegavirales

Paramixoviridae

Boskapspest (Rinderpest)

Giovanni Maria Lancisi

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6 Peste des Petits Ruminants, PPRV

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•Mycket smittsam, ekonomiskt signifikanta sjukdom hos getter och får

• 1940s: Elfenbenskusten i Västafrika (Gargadennec and Lalanne, 1942)

• Morbidity 80-90%

• Mortality 50-80%

• Getter mer mottagliga än får (Nanda och andra 1996)

Peste des Petits Ruminants

• Inkubationstid- 3 to 10 dagar

• hög feber

• nedsatt allmäntillstånd

• seröst nos- och ögonflöde som övergår till att bli purulent.

• munslemhinnan ses hyperemi följt av erosioner.

• djur får en riklig vattentunn, ibland blodblandad, diarré.

• Respiratoriska symtom och tecken på pneumoni förekommer

Peste des Petits Ruminants

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8 Peste des Petits Ruminants

Canine Distemper Virus, CDV

H

Paramyxovirinae Morbillivirus Mononegavirales

Paramixoviridae

Valpsjukevirus

• komplex sjukdom- enterisk, respiratorisk, lymfoid, neural

• Carnivorer – Canidae (reservoir) – Procyonidae (racoons) – Mustelidae (ferrets, mink) – Ailuronidae (pandas)

– Felidae (Panthera, stora kattdjur)

• marina däggdjur

(video) (video)

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”Nya” Paramyxovirus?

G

Paramyxovirinae Henipavirus Mononegavirales

Paramixoviridae

History

• 1994

– First recognized outbreak – Brisbane, Australia

– Respiratory and neurological disease in horses

• 21 horses sick–14 died

• 2 humans sick–1 died

• 1995: Second human fatality

– Assisted in equine post-mortem in 1994

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10 Horses and Hendra Virus

• rapid onset of illness

• fever (over 40 ˚C)

• rapid deterioration in health

• respiratory signs that include:

– increased respiratory rate – respiratory distress – nasal discharge at death

(sometimes frothy and/or blood stained).

• neurological signs that include:

– depression

– loss of balance, problems getting to feet

– loss of vision in one or both eyes – head tilting, circling

– muscle twitching

Hendra Virus

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Nipah Virus Outbreak

• 1998-1999, Malaysia – Respiratory and neurologic

syndrome in swine – Encephalitis in humans

• More than 250 cases

• More than 100 deaths

01/97 Farm worker hospitalized with viral encephalitis (VE).

10/97 First death (pig-farm worker) from VE.

02/98 3 farm workers develop VE.

11/98 Health Minister declares it ‘Japanese Encephalitis’  mosquito control and vaccine program. But outbreak spreads.

1-2/99 Pig farmers begin ‘fire sales’ of pigs. Outbreak recedes a little.

02/99 Laboratories receive first samples of infected human tissue. “New” virus? Mass pig culling begins. Villagers flee.

03/99 Virus isolated and identified with reagents used to characterize Hendra virus (a recently-identified horse virus, from Queensland).

04/99 ‘Nipah virus’ discovery announced. Culling continues.

05/99 WHO declares outbreak over (265 cases, 40% fatal).

02/00 Last death.

Nipah Viral Encephalitis, in Malaysia

Porcine respiratory encephalitis syndrome

• Fever

• Coughing

• Respiratory distress

• Trembling, head pressing

• Abortions, still births

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12 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

Reservoir

• Flying foxes

(fruit bats, Pteropus spp. ) – Carry the virus

– Are not affected – Virus found in

• Urine

• Partially eaten fruit – Migratory

http://www.about-bats.com/fruit-bats.html

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Dr. Peter Hooper, a pathologist for the Australian government, handling a virus-infected fruit bat.