1. Pathogenesis of veterinary respiratory viruses
PETER H. RUSSELL, BVSc, PhD, FRCPath, MRCVS
Department of Pathology and Infectious Diseases, The Royal Veterinary College,
Royal College Street,
London NW1 OTU.
Web site

2. Objectives Students should be able to:
1. explain how some viruses spread within the respiratory tract whereas others leave it to cause disease elsewhere.
2. describe in outline how host responses, vaccines and maternal antibody influence pathogenesis.
3. evaluate how to determine whether a respiratory tract virus is a primary pathogen or whether it exacerbates bacterial disease or does nothing.
4. compare and contrast acute and chronic virus infections of the respiratory tract.

3. Objective 1. explain why some viruses spread within the respiratory tract whereas others leave it to cause disease elsewhere.
Many viruses first replicate in the upper respiratory tract (URT)
Almost all viruses enter the body via the oropharynx as
droplet or by licking contaminated surfaces. They then replicate in the
URT. Some which replicate only in respiratory epithelial cells can
only spread down the tract e.g. Respiratory Syncytial virus.
The invasiveness of the virus determines how far it goes down
eg FCV remains in the URT and FVR extends to the bronchioles.
Other viruses which can replicate in the reticulendothelial system
use the URT as an entry port eg canine distemper.
EHV 1 and 4) cause a transient rhinopneumonitis with cough
necessitating rest and antibiotic cover. The more virulent
abortigenic strains of equine herpes 1 can also infect vascular
endothelial cells and lymphocytes. They thrombose blood vessels
to cause either a placentitis in the 3rd trimester)- the feared
abortion storm- or hemorrhages in the spinal cord (posterior
paresis).
Avirulent NDV and Fowl Plaque isolates replicate in the URT.
Virulent NDV and FP are able to replicate in the viscera and
neurones; the cleavage site which enables their spike proteins to
uncoil and attach is broken in a wide range of cells.

4. Lesions and location
Lesions are erosions and inflammation. Secondary bacterial infection of the erosions causes mucopurulent exudate.
Locations
(i) The URT includes the conjunctiva and harderian /lacrymal
gland, nasal turbinates, nasopharyx, tonsils and mandibular LN,
trachea, sinuses. and
(ii) Bronchi and bronchioles, loss of ciliated cells and mucociliary
blanket and exposure of the basement membrane for the lodgement
of bacteria. There may be an production of proinflammatory
cytokines (IL-1, TNF-alpha) with local ingress of neutrophils and
fibrinous exudates and pyrexia. These block the bronchioles and
thicken their walls.
(iii)Alveoli, thickening of alveolar walls, interstitial pneumonia,
fluid production, secondary bacterial pneumonia.eg porcine
respiratory and reproductive syndrome.
(iv) Draining lymph nodes, T lymphocytes are the site of latency
of respiratory herpesviruses. The herpesvirus genome is
integrated into host DNA w/o being translated until the host is
stressed.

5. Disease is compounded by stress whether crowding, transport or social
Disease is compounded by stress whether crowding, transport or social. The contact allows more interchange of viruse eg Battersea dogs home. The stress reactivates viruses eg herpesviruses or increases virus excretion eg feline caliciviruses. Think of examples for calves, pets, horses.
Many resp diseases involve more than one virus and intercurrent
bacteria.
In pigs resp disease is complex and multifactorial,
eg circovirus causes a general immunosuppression, PRRS causes
a resp tract necrotising pnemonia and then Haemophilus parasuis
finally kills the pigs.
You will learn about examples for calves, pets, horses in the next
2 weeks.

6. Objective 2. describe in outline how host responses, vaccines and maternal antibody influence pathogenesis.
Host responese.
Nonspecific: The infected cells produce interferon curtails
virus replication in the adjacent respiratory epithelial cells.
Interferon also spreads enters to the circulation for 2-4
day and activates splenic NK cells. Specific and memory:
Local cytotoxic T cells abort the production of virus and
neutralising antibody prevents virus spread so the infection
may be stopped by 6 days. The viruses which depend much
on Tc to clear them eg RSV and herpesviruses are those for
which vaccination has been least successful.
With RSV it is been difficult to induce local cytotoxic T cell
immunity w/o DTH-type T cells worsening the lung lesion. This is
why no human anti-RSV vaccines are licensed.

7. Antigenic variation can explains vaccine failures when a new isolate of the same virus arrives eg when the 1998 USA-like strain of equine influenza II (H3N8)entered the UK. Variation can mean vaccines partially protect eg with feline calicivirus. These cats can be silent carriers of the antigenically-distinct FCV and then can enter a cattery undetected and cause lesions in unvaccinated cats (cf FMDV).
Examples of live intranasal vaccine viruses which induce
secretory antibody IgA (or IgG in bovines).
Bovines, temp-sensitive bovine IBR and PI3. These are
genetically-selected and cannot spread down to the bronchioles,
why?
Cats Live intranasal feline herpes and caliciviruses . These are
no longer listed in IVS for UK, perhaps because they have caused
disease when given to kittens of less than 12w old or in kittens with
FeLV, FIV. Live viruses by the subcutaneous route can also cause
disease in kittens if they enter the URT inadvertently e.g. by
grooming
Poultry
Eyedrop/aerosol/water vaccines are widely used in the poultry
industry in the UK. Interestingly we found that the eyedrop
route was much better than the intranasal route because the
conjunctiva is continuous with the duct of the lympho-acinar
Harderian gland (HG). Virus infects the surface of the duct
wall to enter a region full of many IgA-producing cells.
60% of all USA chicks are now injected in-ovo (18d of
embryonation) with live vaccines and Newcastle disease by
conveyor belt to avoid handling chicks on arrival at the farms.

8. How do dead subcut vaccines protect
How do dead subcut vaccines protect? Via circulating IgG which leaks into the inflamed resp tract
Maternal antibody IgG enters via Fc receptors and then becomes
systemic with some leakage into the resp tract. This is why
chickens need to be repeatedly vaccinated against NDV.
In an endemic situation maternal antibody , IgG, will delay virus
replication in animals. The animals develop subclinical disease
when a few weeks old instead of clinical disease when a few
days old e.g. Porcine respiratory and reproductive syndrome (PRRS).

9. Objective 3. evaluate how to determine whether a respiratory tract virus is a primary pathogen or whether it exacerbates bacterial disease or does nothing
Your ideas please!
Key words, Koch postulates, germ free animals, avirulent viruses
(adeno and reovirusea) or those with a range of virulence
eg feline calicivirus, intercurrent infections, stress

10. Objective 4. Compare and contrast acute and chronic virus infections of the respiratory tract.
Acute disease
Example 1) Equine influenza /bovine parainfluenza virus 3 without
intercurrent infection. The animal is virus-positive for 2-7 days
and the damaged epithelium then regenerates
Example 2) Acute virulent avian influenza- the virus replicates
fast in the URT and spreads to the viscera and the birds can die
within a few days.

11. Objective 4. Compare and contrast acute and chronic virus infections of the respiratory tract (Cont.)
Chronic disease
Virus AND disease persists and animal does
not recover for several weeks or never
Example 1) Visna Maedi virus causes a slow immune complex disease
with cellular infiltration of the lungs (or brain and joints) following
repeated bouts of replication in macrophages by antigen variants
of this lentivirus (cf HIV).
Example 2) Sheep pulmonary adenomatosis virus, (Jaagsieke) causes
slow large tumours of the alveolar lining cells with death at 3-4y,
common, no diagnostic test apart from the wheel barrow test.
Example 3) Sendai virus of mouse colonies, (parainfluenza virus1)
causes chronic lung lesions which interfere with slide reading of
carcinogenecity tests. Only use rodents from colonies that are
certified free of antibodies to Sendai
Now you compare and contrast them

12. Further reading Refs. and website
Allan and Ellis, 2000, Porcine circoviruses: a review, J Vet Invest,
12(1), 3-14
Bryson, 1999, Update on Calf Pneumonia, CPD Vet Med 1(3) pp
90-94, Rila publications.
Bryson et al, 1999, Calf vaccines, Vet Rec 145,33-39
Carter, Chengappa and Roberts (The virologist absent from
4th ed) Essentials of Veterinary Microbiology, Vth ed, Section
V on respiratory infections by species
Current index of veterinary specialities (IVS) for details of
vaccines, (I checked to find no intranasal feline vaccines now
listed)
Dawson, Gaskell and Jarrett, Vaccination in cats-an update,.
In Practice, Feb 1999

13. Further reading (Cont.)
Refs. and website
Gaskell and Bennett, Feline and canine infectious diseases 1996
Blackwell
Loeffen et al Survey of infectious agents involved in
respiratory diseases in finishing pigs (Netherlands),., Vet Rec, 145,
Newton et al., 1999, Equine influenza in the UK in 1998, Vet Rec,
145(16)
Radford and Sommerville, 1999, Feline infectious URT disease,
Waltham Focus, 9 (3), pp18-23,
Russell and Edington,Veterinary Viruses, still useful after 15y!
excellent on much else, USA,
sponsored by Bayer

14. Objective 1. explain how some viruses spread within the respiratory
tract whereas others leave it to cause disease elsewhere.
Disease is compounded by stress whether crowding, or what
else……………………………

15. Objective Objective 2. describe in outline how host responses, vaccines and maternal antibody influence pathogenesis.

16. Click for larger picture
Host responses
Vaccines
Maternal antibody
Click for larger picture

17. Your ideas please! Key words, Koch postulates, germ free animals,
Objective 3. evaluate how to determine whether a respiratory tract virus is a primary pathogen or whether it exacerbates bacterial disease or does nothing

18. ) Objective 4. Compare and contrast acute and chronic virus
infections of the respiratory tract.
Us these examples to do your answer PI3= para influenza 3;(FP=fowl plaque= acute avian influenza).

19. Click for larger picture
Us these examples to do your answer PI3= para influenza 3;(FP=fowl plaque= acute avian influenza)
Click for larger picture

20. Us these examples to do your answer PI3= para influenza 3;(FP=fowl plaque= acute avian influenza)