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Small, intermediateDNA viruses

Cell, tissue and host tropism of viruses : disease

Immune evasion by viruses

Emerging viral diseasesViruses as

prophylactics/therapeutics

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Themes

1. 1.     Cell, tissue and host tropism of viruses2. 2.     Arthropod transmitted viruses3. 3.     Cancer-causing (oncogenic) viruses4. 4.     Antigenic variation5. 5. Persistent infections6. 6.    Pathogenic variants generated in situ7. 7.    Zoonotic infections8. 8.    Emerging and re-emerging viral diseases9. 9. Immune evasion by viruses

10. Viruses as prophylactics/therapeutics

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Adenoviruses Adenoviruses aden = gland (Greek)aden = gland (Greek) Key Features:

1. Icosahedral capsid (80 nm)

2. Larger dsDNA genome (35 kbp): 30-40 genes

3. Encodes own DNA polymerase and factors that regulate cellular processes

4. Many animals are infected by multiple serotypes

5. Mainly associated with mild respiratory disease

6. Highly immunogenic. Fairly resistant

Adenoviruses

first isolated from adenoid tissuefirst isolated from adenoid tissue

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Adenoviruses

Adenovirus StructureAdenovirus Structure

hexonpentonfibre

terminal protein

DNA

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Adenoviruses

Importance of Adenoviral capsid

1. Fibre and penton bind to proteins on the cell surface- determine tissue infectivity.

2. Adenoviruses can cause red blood cells to clump (haemagglutination). Mediated by the fibre. Used for diagnosis- haemagglutination-inhibition (HI) test.

3. Hexon is the most abundant capsid protein and the major target for the infected animal’s immune system. Immunity is long-lasting.

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Adenoviruses

1. Can infect quiescent cells and “push” them into cell division – promotes availability of factors for DNA replication and protein synthesis

2. Express proteins which favour virus replication, transcription and translation over those of host cell

3. Express proteins which impede the host animal’s immune system, allowing the virus more time to grow and disseminate1. transcriptional repression of MHC genes2. Inhibition of trafficking of MHC3. Downregulation of apoptosis4. Interfere with cytokine function (e.g. TNF-alpha,

interferon)

Immune evasion

[ Theme : immune evasion ]

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Adenoviruses

Veterinary adenoviruses

1. CAV-1 was one of the first adenoviruses to be identified. Isolated in 1954 as the causative agent of infectious hepatitis.

2. CAV-1 also causes respiratory, renal, ocular disease, systemic disease (puppies).

3. CAV-1 infects other canids - cause of fatal encephalitis in foxes.

5. Both viruses are most serious for unvaccinated puppies.

4. CAV-2 associated with respiratory disease - component of kennel cough. Causes tonsillitis, pharyngitis, tracheitis, bronchitis, and bronchopneumonia

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Adenoviruses

Avian Adenoviruses

1. Egg drop syndrome (EDS76)- first reported in 1976. Infects pouch shell gland with soft-shelled and shell-less eggs produced, with no clinical signs.Effectively eradicated from most countries.

2. Turkey adenovirus 2- haemorrhagic enteritis of turkeys and marble spleen disease of pheasants. Also causes immunosuppression. Controlled by vaccination.

3. Avian adenovirus 1- causes bronchitis in quails. Control by isolation and decontamination.

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Theme : viruses as therapeutics

vaccine vectors – delivering genes encoding important antigens of other viruses (e.g PRV gD, FIV env)

gene therapy vectors- delivering therapeutic genes -replacement of genetic deficiency - promoting cytotoxicity (to kill tumours) - promoting amelioration of disease

Adenoviruses

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Adenoviruses

Summary of AdenovirusesSummary of Adenoviruses

1. Larger (26 to 45 kbp), more complex genome than parvoviruses.

2. Encode factors which allow them to manipulate the host- stimulating cell division, controlling cellular processes and avoiding host immune responses.

3. Fibre binds cell receptors, can cause haemagglutination

4. Hexon is the major target of host immune system. Immunity is robust and long-lasting.

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Parvoviruses Parvoviruses parvus = small (latin)parvus = small (latin)

Key Features:1. Icosahedral capsid (20 nm) [no envelope]

2. Small, linear ssDNA genome (5 kb)

3. Infect and kill dividing cells

4. Persist for long periods in the environment (extremely resistant to heat and to high or low pH)

5. Cross placenta, causing infection of the foetus

6. Generally species-specific (but interspecies transmission between carnivores)

7. Generally cause disease in YOUNG animals

Parvoviruses

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1. Feline panleukopaenia virus (FPV)

2. Canine parvovirus (CPV)

3. Goose parvovirus (GPV): lethal in young goslings causing hepatitis and myocarditis.

4. Bovine parvovirus: diarrhoea in calves

Parvoviruses

Infect dividing cells – generalised disease in fetus/newborn, enteritis, leukopaenia

Members of veterinary importance

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Parvoviruses

Feline parvovirus (FPV)

1. Also known as feline infectious enteritis, or feline panleukopenia

2. Infects lymph nodes of nasal- and oral-pharynx, then spreads to other tissues

3. Kittens most susceptible. However unvaccinated older cats can be infected. Problem with infected pregnant queens (wobbly kittens)

Pathogenesis

1. Panleukopenia- decreased white blood cell count, killing of lymphoid and myeloid stem cells

2. Enteritis- killing of stem cells in crypts [dehydration]3. Cerebellar hypoplasia- infection of germinal epithelium of

neonatal kittens [+/- 2 wks birth]

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Feline parvovirus infectionParvoviruses

Parvovirus growsin dividing stem cells

in the crypts

Scanning electron micrographs : small intestine

normal

FPV infected

enteritis

Villi tip cells which die naturally can’t be replaced as FPV has killed stem cells – stunted villi, malabsorption

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Cerebellar hypoplasia

Feline parvovirus

Normal kitten

Feline parvovirus infectionParvoviruses

Cerebellum – controls coordination/balance

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Parvoviruses

CPV-2

CPV-1 – minute virus of canines – mild diarrhoea

Canine parvoviruses

New viruses causing disease or existing viruses which now cause increased disease (in same or new host)New/increased exposure to host harbouring virusMutation of virus (+ adaptation to new sp)

[THEME Emerging disease ] First identified in Europe in

1978Rapidly spread worldwide

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Parvoviruses

Pathogenesis: infection of rapidly dividing cells

1. Enteritis [blunted villi]

2. Leukopenia

3. Myocarditis in neonatal puppies

Canine parvovirus 2

Cause of ‘fading puppies’

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ParvovirusesCanine parvovirus infection

NormalCPV infected (unvaccinated mother)

Grossly dilated ventricles

Heart failure due to myocarditis (inflammation of heart muscle)

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Parvoviruses

Diagnosis and control of FPV/CPV

1. Vaccinate : Modified live and inactivated virus vaccines available : boost every 1-2yrs (Maternally derived antibody wanes after about 8 weeks)

2. Management : Prevent exposure of kittens/puppies to PV in environment (premises/outdoors/animals)

[virus survives for months]

Faeces (high levels of virus) – virus detectionBlood sample – parvovirus antibody detection

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ParvovirusesSummary of ParvovirusesSummary of Parvoviruses

1. Small linear ssDNA genome.

3. Emerging viruses- CPV-2. Cross-species transmission.

2. Virus requires actively dividing cells + can cross placenta - reflected in pathogenesis - young animals most susceptible

4. Only a few amino acid changes in capsid protein required for altered host range/pathogenicity.

5. Stable in the environment - rigorous cleaning and disinfection required following outbreak.

6. Control – vaccination (+ management)