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Notities Research track advances in pandemic preparedness
- Établissement
- Katholieke Universiteit Leuven (KU Leuven)
Notities van de research track advances in pandemic preparedness
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1Definitions
- Shedding
- Host adaptation
- Recombination
- Species barrier
- Reservoir = environment in which a pathogen naturally lives
- Virus evolution
- Cultivation system
- Environmental persistence
- Replication
- Serology
- Aerossol
- Permissive cell has the capacity to replicate virus. <-> abortive
- Susceptible individual = individual with cells that have the receptor. A virus can enter
a susceptible cell, but it cannot replicate. <-> resistant
- Vector
- High fidelity = copy looks like the original
- Infectious virus = virus that can make you sick. Virus is infectious or not. Viral RNA is
not infectious virus.
Transmission
- Forms of transmission:
- Airborne: droplets, aerossol (smaller - travel longer through the air - more
dangerous)
- Formite transmission: bacteria or virus remain on surface and cause infection
- Fecal oral transmission: foodborne (contaminated food), waterborne (drinking
contaminated water, swimming)
- Bloodborne: transfusion, needle stick injuries
- Vertical transmission: transplacental, perinatal
- Mucosal / skin to skin
- Vector: mosquitos, ticks, midges
- From human to human (people in your household, places with a lot of people,
hospital staff, food handlers)
- From animals (domestic animals, wild animals, pets, rodents, mice (via urine or stool
- aerosolization or touch it)
- What boosts transmission?
- Behaviour
- Occupational hazards
- Forest worker - more exposed to animals
- ..
- Overpopulation
- Transport
- Immune deficiency
- Bad healthcare
- Pregnant woman
- Immune status, not vaccinated of yourself or of your community
, - It is often a combination of different routes of transmission
Questions
- An abortive infection is one that progeny virus is not produced
- Which of the following virus types has nucleic acid functions directly as mRNA?
Single stranded positive sense RNA viruses
- The genome of a known RNA virus could be any except ds circular
- Most enveloped animal viruses may enter the host cells by endocytosis
- Virus particle = virion
- A structural component that is found in all viruses is the capsid
- envelope = green
- What is the most common cause of aseptic meningitis of viral etiology? enteroviruses
- Which one of the following infection routes are most often involved in the neonatal
transmission of hepatitis B virus (HBV)? Fetal contact with infected blood during
childbirth
- The finding of large, multinucleated, clumps of cells in the bronchial secretions of a
2-year-old girl with acute bronchopneumonia suggests that this infection is caused by
RSV
- What does the reproductive number of a virus tell us? How many contacts will be
infected from one case, R0
- How are arenaviruses spread? Aerosols of urine from infected small animals
- Which is a major characteristic of the bunyavirus family? Amplify by persistent
infection of midges, mosquitoes, sand flies, ticks
,2
Difference between endemic, pandemic and epidemic
- Disease that is present = endemic
- A lot of cases, big increase as compared to before = epidemic
- Epidemic spreads globally = pandemic
Zoonoses
- Spillovers are a growing threat
- = infectious diseases that can spread from animal to human
- They are clinically important.
- Important to control diseases in animals. Consider health as a whole. Better control
of disease in animals - we will be less vulnerable. Focus on prevention.
Type of hosts
- Natural host:
- Some of the viruses have a natural host
- Virus can circulate but no disease
- Example, bats, waterbirds
- Secondary transmission host
- Animal that is close to us
- Disease
- End / spillover host
Major diseases of animal origin affecting human health
When we see a virus emerge in a region we should assess what is the risk for the rest of the
world.
Spillover and cross species transmission
Spillover from natural host - reach domestic animals - further potential for amplification in
domestic animal - increased risk for spillover to humans
Spillover to humans via natural host or via domestic animals
Transmission via a vector or from human to human
Good surveillance, fast respons - we see the little spillover event, we are aware - limit the
spread in domestic animals - limit the spillover to humans
5 stages through which pathogens of animals evolve to cause disease confined to
humans
Stage 1: agent only in animals
Stage 2: only from animals
Stage 3: from animals to humans + little human to human transmission
Stage 4: spillover from animals to humans + sustainable circulation in humans
Stage 5: evolved to human to human transmission
Determinants of cross species transmission or spillover
When is it more likely to happen based on what already happened?
- RNA viruses rather than DNA viruses
- Varies among host species owing to differences
, - Viral richness is high for bunya, flavi and arenaviruses in rodents, high
number of these viruses in rodents. They can eventually spillover to humans
- Opportunity for contact with humans
- …
- We have to worry certain animal reservoir more in certain locations
Viral traits = traits that predict zoonotic potential of a virus
Which viruses can affect the widest variety of species? These might affect humans as well
Routes of transmission
- By direct contact with animals
- ..
Depends on the virus
The error prone replication of RNA viruses
How viruses challenge their genome, how can some do more than others?
- RNA dependent RNA polymerases are error prone
- Most RNA viruses cannot use the proofreading machine or encode for a protein with
this function
These 2 features results in the fact that RNA viruses have a higher mutation rate
Coronaviruses have the proofreading capacity.
Mutations can be deleterious, neutral or beneficial
- Bad - harm the virus, difficult to infect new cells - extinguish themself
- Neutral
- Good
Balance is important. The more mutations - the more there is a cost of fitness. Mutant
viruses pay the price in terms of fitness.
Viral RNA polymerases
- Template channel, incoming nucleotide channel and out channel
- Conserved motifs indicated with letters
- Catalytic site is the most conserved throughout all viruses - is a very good
target for inhibitors
Genetic recombination
- 2 possibilities
- Self recombination
- Recombination with host
- Much less common
- In bigger viruses
- How does this happen? Via template switch or via virus RNA breakage
- Many factors affect genetic recombination
- Different consequences
Reassortment and genetic shift
- When 2 segmented viruses infect the same cell
- Genetic reassortment causes major changes resulting in a genetic shift.
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