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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