Lec 12 Parvoviruses and Circoviruses Flashcards
Parvovirus
Small virus and small genome, non enveloped
1.7kb ambisense, circular ssDNA genome
3 major genes (cap, rep[‘], orf3)
4 major gene products accommodated over several ORFs
Icosahedral, non-enveloped, only one structural protein (capsid [cap])
Shed near nasal and waste environments, easily transmitted to other pigs in filthy environment!
“Dirty” environment: feces contain bacteria that serve as reservoirs for the viruses when outside the pigs.
*Non-enveloped viruses are more stable than enveloped viruses in the environment, in general!
Tenacity: stabile at pH 3, 70°C 15 min., Virkon 10 min.
Porcine circovirus associated diseases - PCVAD
Porcine circovirus associated diseases - PCVAD
Smallest viruses that can replicate alone w/o the need of host machinery.
PCVAD are globally distributed
Model for immunosuppressive disease
Molecular pathogenesis of disease is unknown
Infects primarily B cells in pigs, at least 1 timer per life time. D.t. unavability of vaccinations this causes serious harm.
Life cycle
In such small viruses there is no overlap of functions.
Viruses with a small genome: which functions must be encoded?
Attachment?
Entry?
Genome replication?
Viral gene expression (proteins): completely from the host transcription and translation.
Assembly: 1 capsid protein wraps around genome.
Egress?
Major fear of virus: be destroyed by host endonucleases. Must become invisible.
PCVAD - Pathogenesis
Some pigs carry the infection for most or their entire life! 40% of pigs are infected in Alberta. Infection pathology and disease this way are unknown.
PCV2 + Immunostimulant. The virus replicates to high titers, high loses of lymphocytes (immunosuppression), Leads to disease
(Infection, [non-PCV2] vaccination, mitogen)
Vaccinate the hell out of the pigs.
You do NOT vaccinate immunosuppressed animals:
- Insufficient response by the immune system
- Live attenuated virus will cause damage
The pigs become susceptible to viruses, bacteria, especially piglets (measles: diarrhea, respiratory)
What are the criteria for virus classification?
A close relationship of two or more viruses – what could that mean?
Looking at this picture of viruses from different families – what is an obvious difference of circo viruses in comparison to influenza, retro and herpes viruses?
What are the implications of this difference?
What are the main target cells for HIV and for influenza virus? Why is this important?
What are the criteria for virus classification?
How mRNA are made.
A close relationship of two or more viruses – what could that mean?
- Evolution similarity,
- Horizontal gene transfer (recombination)
- Proteins w/ similar functions => similar disease outcome
- Similar target cells, immunological similarities
Looking at this picture of viruses from different families – what is an obvious difference of circo viruses in comparison to influenza, retro and herpes viruses?
- Whether proteins cover the capsid or not
- HOW it ENTERS the CELL (enveloped/non-enveloped)
What are the main target cells for HIV and for influenza virus? Why is this important?
- CD4+ T cells (lymphocytes). HIV causes immunosuppression and deficiency. Porcine Circoviruses also cause immunosuppression.
- Influenze mainly targets the respiratory epithelial cells. Porcine Circoviruses also target these.
Circoviruses - summary
Very small viruses, found in many species
Non-enveloped, very robust
Only one structural protein (capsid)
Two or more non-structural proteins
ss-stranded circular 1.8kb DNA genome
Diseases in birds and pigs
Viral replication in tissue with high mitotic rate
Parvoviruses
Why in young animals?
Found in all mammals.
Main problems in children, young cats and dogs. Fetuses and young animals have high mitotic rates in many organs, and this accelerates viral replication!
Parvovirus physiology
Family = Parvoviridae Subfamily = Parvovirinae Genus = Parvovirus Host = Swine
Distribution: endemic in most herds worldwide
Viral Characteristics: Non-enveloped, small (-) ssDNA virus, spherical, 20-26nm in diameter, replication is cytocidal, no essential lipids or glycoproteins
Residues on surface of capsid differ from other parvoviruses
Different host ranges and clinical presentations
Neutralizing antibodies targeted against capsid structural proteins (VP2)
Disease in Pigs
Targets rapidly dividing cells
Acute infection of postnatal pigs = subclinical (transient leukopenia)
Suckling pigs: can see skin lesions, non-suppurative myocarditis, diarrhea?
Slaughter pigs: interstitial nephritis
Reproductive failure in naïve dams
Main Significance = Reproductive Failure NOT diarrhea
Same routes of transmission and circoviruses
Oronasal: post-natal pigs
Direct: acutely infected pigs shed virus for up to 2 weeks
Indirect: infected viral particles in environment
Transplacental: pre-natal pigs
Venereal: boar semen (acute infection)
Mechanical: boar acts as vector (not acutely infected)
Viral Reservoir = Contaminated Environment
Vey stable, can remain infectious outside host for at least 4 months
Semen is vulnerable to viruses because the glands that produce sperm are secluded from the immune system.
Transplacental Infection
Targets for this viruses are not protected. Vaccination is life long protection.
Seronegative dam (usually 1st parity sow) infected during first half of pregnancy
Passive immunity interfering with vaccination (development of active immunity)
Outcome dependent on when dam is infected during gestation
Death and resorption
Mummification!
Immune response and survival
3 trimesters
- Few cells die. Embryonic death and resorption, sow presents as return to estrus or fewer pigs per litter.
eg. piglets produced / year decreases - Fetal death and mummification.
- Fetus immunocompetent, mounts immune response and survives. Piglet in eutero is somewhat immunocompetent (in pigs!) and can fight infection.
Why is the outcome of porcine parvovirus infection of naïve sows not uniform, i.e. death and resorption, mummification, survival of piglets?
Why is the outcome of porcine parvovirus infection of naïve sows not uniform, i.e. death and resorption, mummification, survival of piglets?
The virus hits the immunogically weak cells, the virus goes from piglet to piglet, they are not all exposed at the same time so transmission is slow!
Its easy to determine that parvoviruses are behind this,
Circovirus, parvovirus replication cycles
Both need rapid host DNA replication.
Helicase unwinds the chromatin (condensed dsDNA)
Both viruses need to make dsDNA from DNA dependent DNA pol in host to make genome. Make nicking (nickase) and DNA pol (rolling circle).
DNA dependent DNA pol is most dependent in S phase in mitosis. To increase viral replication they arrest the cell in S phase by messing with the Cdk concentrations! 411
The virus encodes the helicase and otherwise heavily on host enzymes.
Baltimore classification of viruses
Pathways of primary mRNA synthesis by DNA viruses of animals
This all happens in the nucleus.
Once enough newly made viruses have accumulated, the structural proteins are made by translating the mRNA
mRNA is made in RNA pol 2, template is dsDNA
Most DNA viruses replicate in the nucleus.
Most RNA viruses replicate in the cytoplasm (exception retrovirus)
Machinery brought to cytoplasm from viral encoded proteins,
