1

RNA viruses

pathogenic variantspersistent infectionsEmerging virusesAntigenic variationZoonotic disease

2

Orthomyxoviruses

segmented RNA genomes – 8 segments; 14 kb

2 envelope glycoproteins - haemagglutinin and neuraminidase (key targets of humoral

immune responses) Influenza viruses cause serious respiratory

and systemic disease in animals and man Major antigenic shift may be associated

with genetic reassortment between strains of virus

ss RNA enveloped, helical nucleocapsid, pleomorphic 100nm

myxo = mucus

3

Orthomyxovirus Structure

-ss RNA matrix proteins 2 envelope glycoproteins haemagglutinin (H or HA)

receptor binding uncoating

neuraminidase (N or NA) release receptor binding

4

Orthomyxovirus Replication

HA :sialic acid

RNA synthesis

- transcription

- replication

viral polymerase

nucleus

antiviral drugs applied inhuman medicine

blocked byamantadine- target M2

blocked by Tamiflu - target neuraminidase

virus assembly

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Isavirus genus• Infectious salmon anaemia• Emerging disease in farmed salmon : 1984 (Norway)• Scotland 1998/9 £20Million, eradicated

important genera : Influenza A (avian/mammalian) Isavirus (fish)

Veterinary Orthomyxoviruses

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wild aquatic birds (waterfowl and shorebirds)– alimentary tract

infection largely asymptomatic

transmitted faecal/oral route (waterborne)

ALL H [16H types] and N [9N types]

Influenza A : Reservoir -

Influenza A viruses

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Influenza A viruses

infection of mammals usually restricted to respiratory tract

transmitted by aerosol Limited H and N types

Equine influenza -Swine influenzaFowl plague - NOTIFIABLE

Human influenza [Theme - Zoonosis]

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N1N2N3N4N5N6N7N8N9

H1

H3H4H5H6H7H8H9H10H11H12H13H14H15

H2

Aquatic avian species - all H,NMan, pigs, horses limited H,N types

H and N types in various species

H16

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Antigenic ShiftAntigenic Shift

Antigenic DriftAntigenic Drift spontaneous mutations in surface antigens selection ofvariants in a partially immune population

new strain

H1N1

H2N2

circulating human influenza strain

avian influenza strain

Reassortment

H2N2

major change in surface antigenicity - associated with reassortment (or recombination)

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Transmission of Influenza A

wild/domestic birds

man

pigs

known?

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Equine influenza

First isolated 1956 Two subtypes : H3N8, classical H7N7

Swine Influenza

First observed 1918 U.S. during Spanish flu.Currently circulating strains are H1N1 (avian derived), and H3N2 and H1N2 (human-like reassortant strains)

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Spanish flu [1918]

killed more people than 1st World War

high mortality rate

killed young and healthy

Emergency hospital during influenza epidemic, Camp, Kansas

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Highly Pathogenic AI(HPAI, Fowl Plague)

Pathogenic H5 and H7 strains of avian influenza virus Affects turkeys, chickens with mortality up to 100% NOTIFIABLE:

Control : culling (affected farms + 3km radius), isolation of waste, restriction zones, disinfection of premises

In infections with the most virulent strains there is viraemia and multifocal lymphoid and visceral necrosis, leading to pancreatitis, myocarditis, myositis, and encephalitis. Chickens and turkeys succumbing after several days of illness exhibit petechial hemorrhages and serous exudates in respiratory, digestive, and cardiac tissues. Turkeys may also have air sacculitis and pulmonary congestion.

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H5N1 spread: poultry & wild birds 2003-2007

>200 millionPoultry culled

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Human influenza virus pandemics

exposure to influenza virus (of different antigenic type) circulating in another species [1] which can replicate and cause clinical disease in man [2] - transmission from pigs infected with human/animal/avian reassortants - adaptation of avian virus in pigs (or in humans) - direct transmission (e.g. birds to man) [re-emergence from environmental reservoir] adaptation, drift, shift in new host [3]

World-wide surveillance of influenza outbreaks in man/animals/birds : World Health Organisation

Pandemic : virus must transmit efficiently between humans

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Human Influenza

Pandemics1957asian

1968hong kong

H1N1 no longer circulating

H2N2 no longer circulating

H1N1H3N2

H1N2

1918spanish

H1N1[Avian]

H1N1

H2N2[Avian]

H2N2

[Avian]

H3N2

H3N2

[1977]

In currentcirculation

1763% mortality rate by H5N1 in humans

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CORONAVIRUSES

corona = crown (latin)

Helical nucleocapsid

Membrane

Spike

Positive sensesingle stranded RNA

Enveloped 120nm, positive sense ssRNA with helical nucleocapsid.

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Key features

1. Associated mainly with enteric and respiratory diseases. The most important are infectious bronchitis of chickens and feline infectious peritonitis of cats.

2. The envelope glycoproteins as very conspicuous, petal-like structures called peplomers. The consequent distinctive crown (corona) -like structure gives the group its name.

3. Very prone to mutations affecting antigenicity and virulence.

4. Diagnosis: don’t generally grow in cell culture - therefore use serology, histopathology, RT-PCR

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B & C: ADE, absorption

requires only Fc receptor

A: normal infection,

attachment to cellular receptor

Some FCoV vaccineshave enhanced ADE (and disease) on challenge

Immunne evasion

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Coronaviruses

CHICKEN

DOG

CAT

HUMAN

respiratory/urogenital

intestinerespiratory

intestine/macrophages

respiratory

IBV

FCoV

HCV 229EHCV OC43SARS

CCoVCRCoV

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Infectious bronchitis IBV is a commercially very important disease of both broilers

and layers. The virus replicates in the respiratory and urogenital tracts. In chicks I to 4 weeks of age, virulent virus strains produce

gasping, coughing, rales, nasal exudate, and respiratory distress. Young chicks may develop a severe tracheitis with a mortality rate of up to 90%.

Chick layers that survive may have defects in the oviduct that prevent egg production in the adult bird.

Primary infection of adult laying birds may not be associated with clinical signs but infection of the oviduct leads to a severe drop in egg production and the eggs are often misshapen and soft-shelled.

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Canine coronaviruses

Canine enteric CoV CECoV (CCoV) – types I, II Canine respiratory CoV (CRCoV) [group 2] - ‘discovered’ 2003 Involved in canine infectious respiratory disease

with CHV, CAV-1, canine parainfluenza virus + other agents

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Feline coronaviruses

BiotypesFECV (FCoV) feline enteric coronavirusFIPV feline infectious peritonitis virusGenotypestype 1, type 2

Most infections are inapparent or result in mild diarrhoea.The virus normally grows in the intestinal tract and is shed in the faeces.Carrier cats are important in transmission.Occasionally an infected (seropositive) cat develops FIP

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Atchoo!

0

FCoV shedding in 70% of exposed cats

Months

2d p.i.

18-21d

uninfected

infected

infectedinfected

The main source of FCoV infection is contact with faeces or the used cat litter of infected cats.FCoV can survive up to 7 weeks in dried up cat litter.

15% cats become lifelong FCoV shedders

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FCoV

FIPV

wet dry

Replication in macrophages

Immune complex formation in blood vessels

Immune mediated vasculitis

Mild/subclinicalenteritis

Pathogenesis of FIP

Clinical forms FIPEffusive (wet)Non-effusive (dry)

Coronaviruses mutate/recombine easily giving rise to different biotypes

FCoV I/CCoV II FCoV II

FCoV FIPV ?

Mutation within infected animal to generate pathogenic strain

Theme: Emerging virus

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SARSSevere acute respiratory syndrome : SARS-CoV

2002-2003 asia –> spread to americas, europe 800 deathsPossible source : CoV of palm civet – from bat?

man

~90% sequence identity