RNA viruses
pathogenic variants
persistent infections
Emerging viruses
Antigenic variation
Zoonotic disease 1
Orthomyxoviruses
ss RNA enveloped, helical nucleocapsid, pleomorphic 100nm
myxo = mucus
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
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Orthomyxovirus Structure
-ss RNA
matrix proteins
2 envelope glycoproteins
haemagglutinin (H or HA)
receptor binding
uncoating
neuraminidase (N or NA)
release
receptor binding
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Orthomyxovirus Replication
HA :sialic acid
blocked by
RNA synthesis
amantadine - transcription
- target M2
- replication nucleus
viral polymerase
virus assembly
antiviral drugs applied in blocked by Tamiflu -
target neuraminidase
human medicine
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Veterinary Orthomyxoviruses
important genera : Influenza A (avian/mammalian)
Isavirus (fish)
Isavirus genus
• Infectious salmon anaemia
• Emerging disease in farmed salmon : 1984 (Norway)
• Scotland 1998/9 £20Million, eradicated
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Influenza A viruses
Influenza A : Reservoir -
wild aquatic birds (waterfowl and shorebirds)–
alimentary tract
infection largely asymptomatic
transmitted faecal/oral route (waterborne)
ALL H [16H types] and N [9N types]
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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 influenza
Fowl plague - NOTIFIABLE
Human influenza [Theme - Zoonosis]
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H and N types in various species
H1
H2 N1
H3 N2
H4 N3
H5 N4
H6
N5
H7
H8 N6
H9 N7
H10 N8
H11 N9
H12
H13 Aquatic avian species - all H,N
H14 Man, pigs, horses limited H,N types
H15
H16
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Antigenic Drift
spontaneous mutations in surface antigens selection of
variants in a partially immune population
Antigenic Shift
H1 H2 H2
N1 N2 N2
Reassortment
circulating avian new strain
human influenza
influenza strain
strain
major change in surface antigenicity - associated with
reassortment (or recombination)
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Transmission of Influenza A
wild/domestic
birds
man
known
? pigs
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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:
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.
Control : culling (affected farms + 3km radius), isolation of waste,
restriction zones, disinfection of premises
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H5N1 spread: poultry & wild birds 2003-2007
>200 million
Poultry 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]
Pandemic : virus must transmit efficiently between humans
World-wide surveillance of influenza outbreaks in
man/animals/birds : World Health Organisation
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Human Influenza Pandemics
1918 1957 1968
spanish asian hong kong
[1977] H1N1
H1 H2 H3
N1 N2 N2
H3N2
H1N2
In current
H1N1 H2N2 H3N2 circulation
[Avian] [Avian] [Avian]
H1N1 no longer H2N2 no longer
circulating circulating
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63% mortality rate by H5N1 in humans 17
CORONAVIRUSES
Enveloped 120nm, positive sense ssRNA with helical nucleocapsid.
Spike
Membrane corona = crown (latin)
Helical nucleocapsid
Positive sense
single stranded RNA
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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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Immunne
evasion
A: normal
infection,
attachment to
cellular receptor
B & C: ADE,
absorption
requires only Fc
receptor
Some FCoV vaccines
have enhanced ADE (and
disease) on challenge
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Coronaviruses
CHICKEN IBV respiratory/urogenital
DOG CCoV intestine
CRCoV respiratory
CAT FCoV intestine/macrophages
HCV 229E respiratory
HUMAN HCV OC43
SARS
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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
Biotypes
FECV (FCoV) feline enteric coronavirus
FIPV feline infectious peritonitis virus
Genotypes
type 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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FCoV shedding in 70% of exposed cats
15% cats become lifelong FCoV shedders
infected
infected
18-21d Atchoo!
0
infected
Months
The main source of FCoV infection
is contact with faeces or the used
cat litter of infected cats.
2d p.i.
uninfected FCoV can survive up to 7 weeks in
dried up cat litter.
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Pathogenesis of FIP
FCoV Mild/subclinical
Clinical forms FIP enteritis
Effusive (wet)
Non-effusive (dry) FIPV
Replication in macrophages
Immune complex formation in blood vessels
Immune mediated vasculitis
wet dry
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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
SARS
Severe acute respiratory syndrome : SARS-CoV
2002-2003 asia –> spread to americas, europe
800 deaths
Possible source : CoV of palm civet – from bat?
man
~90% sequence identity
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