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I&I SC2 > Animal models: virology > Flashcards

Animal models: virology Flashcards

1
Q

What is the definition of an ‘animal model’?

A

Living organism, in which a spontaneous or induced pathological process can be investigated, and in which the phenomenon in one or more respects resembles the same phenomenon in humans

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2
Q

What are animal models historically known for?

A

For obtaining information on physiology and disease

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3
Q

What are animal models heavily regulated by? (3)

A
  • Legislation
  • Guidelines
  • Experimental design requirements
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4
Q

What are the three R’s?

A
  • Refine procedures (most humane way)
  • Reduce the number of animals
  • Replace with non-animal alternatives
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5
Q

Which guidelines can be used for reporting animal research?

A

ARRIVE

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6
Q

Which guidelines can be used for planning animal research?

A

GUIDE

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7
Q

What are important factors when choosing the correct animal model? (3)

A
  • Consider research question
  • Susceptibility, tissue (tropism), clinical signs
  • Comparability human vs. animal
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8
Q

What are important factors to consider about the chosen animal model (6)?

A
  • Age
  • Sex
  • Genetic background
  • Microbiological status
  • Comorbidities
  • Variation
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9
Q

Name general influential factors and important aspects of animal models in virology (5)

A
  • Acclimatization to new housing in animal facility
  • Housing
  • Biology and behavior of the animal model
  • Containment level
  • Sampling (which, when, how often)
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10
Q

Why is acclimatization to new housing in animal facility important?

A

Provides stress-free animals at the start of the experiment

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11
Q

Which clinical signs and clinical scores can be used to measure in animal models in virology? (4)

A
  • Body weight
  • Appearance
  • Behaviour/activity
  • Body temperature
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12
Q

What are ‘other’ factors to consider when choosing an animal model in virology? (3)

A
  • Humane endpoints
  • Anesthesia and euthanasia
  • Post experimental analysis
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13
Q

What is important about anesthesia and euthanasia? (2)

A
  • Should not interfere with read-outs
  • Should not cause excessive discomfort
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14
Q

What factors should be considered about the reagents (vaccines, antivirals, etc)? (4)

A
  • Adjuvant
  • Concentration
  • Route of administration
  • Schedule
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15
Q

What factors do you need to consider when selecting the virus for the experiment? (6)

A
  • Strain
  • Origin and propagation of virus
  • Which titer do you give to animals?
  • Quality of virus
  • Stability
  • Alterations necessary?
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16
Q

Which animal model is often the first choice to study unknown human viruses?

A

Non-human primates (NHP)

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17
Q

Why do you always have to think of different ways to answer the question? (with respect to NHP)

A

NHP are very expensive and ethically questionable

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18
Q

Name River’s modified Koch’s postulates (6)

A
  • Virus isolation
  • Virus propagation
  • Filtration
  • Inoculation of & disease in macaques
  • Re-isolation & PCR of virus from diseased animals
  • Specific immune responses to the virus in animals
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19
Q

Why do you look into specific immune response to the virus in animals?

A

Confirms that agent causes the disease in animals

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20
Q

Name the common animal models for SARS-CoV (4)

A
  • NHP
  • Golden Syrian hamster
  • Ferrets
  • Transgenic mice
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21
Q

MERS-CoV: Why did ferrets not seroconvert after intranasal/intratracheal inoculation with high dose of virus?

A

Ferret DDP4 does not bind MERS-CoV

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22
Q

What can you do if there is no correct animal model?

A

Adaptation of virus to host by serial passaging in host of interest

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23
Q

Summary: name three important factors to consider when choosing an animal model for MERS-CoV experiments?

A
  • Diversity: genomic analysis of different MERS-CoV
  • Receptor: sequence and binding analysis of DPP4 in different animals
  • Host: analysis of the host response in different animals
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24
Q

What are common animal models used for MERS-CoV experiments? (3) Which is most often used?

A
  • Rabbits
  • Healthy, young NHPs
  • Transgenic mice with hDPP4 receptors (most often used)
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25
Q

What can also influence the outcome of experiments?

A

Comorbidities

26
Q

SARS-CoV2: Which factor is very influential in experiments? Why?

A

Propagation –> causes cell culture adaptations in multibasic cleavage site

27
Q

Why happens when there are cell culture adaptations in the multibasic cleavage site? How can this be prevented?

A

Changes infection proficiency/transmission efficiency –> can be prevented through using other propagation systems

28
Q

What are animal models used for SARS-CoV2? Which is most often used? (4)

A
  • Transgenic mouse
  • Hamster (most often used)
  • Ferret
  • NHP
29
Q

Why are hamsters most often used as an animal model for SARS-CoV2? (3)

A
  • Shows clinical symptoms (body weight loss)
  • Viral shedding
  • Replication in URT and LRT
30
Q

What has the hamster model demonstrated? (4)

A
  • Effect of age
  • Effect of sex
  • Effect of comorbidities
  • Effect of precise species
31
Q

What is the main disadvantage of ferrets as a model for studying SARS-CoV2?

A

Only show replication in the URT

32
Q

Describe the new lung xenograft mouse model

A

Human lung is grown in a mouse model

33
Q

What is the main advantage of the lung xenograft mouse model?

A

Susceptible to all human coronaviruses

34
Q

What are the problems in developing an appropriate animal model for zoonotic coronaviruses? (3)

A
  • Viruses are genetically diverse, as they are adapting to a new host
  • Adaptations may affect the interaction with the host
  • Comorbidities influence the outcome of infection
35
Q

Why is using an animal model useful when studying influenza viruses? (3)

A
  • Pathogenesis studies involving pathology are difficult in humans
  • Quality of pathology is low in human fatal cases
  • Cannot study vaccine protection by challenge
36
Q

Influenza: Why are pathogenesis studies involving pathology difficult in humans?

A

People often present to healthcare in a later stadium of disease –> initial pathology hard to study

37
Q

Influenza: by using animal models, we can .. (5)

A
  • Set the timing of pathology
  • Study the course and the evolution of the disease
  • Detect (early) events
  • Have group size to reach statistical significance
  • Challenge with pathogenic strains
38
Q

Influenza: Name model components related to animal species for human disease (5)

A
  • Susceptibility
  • Symptom similarity
  • Anatomy/histology of target organ similarity
  • Immune response/status similarity
  • Cell tropism of pathogen similarity
39
Q

Name examples of aspects of disease that you could try to reproduce in the animal model (4)

A
  • Pathology
  • Interplay between pathogen and immune system
  • Transmission
  • Vaccination
40
Q

Influenza: which pathogen characteristics do you need to consider? (4)

A
  • Passage history
  • Wild-type vs. recombinant
  • Dose of inoculum
  • Volume of inoculum
41
Q

What is important to consider when using a wild-type virus?

A
  • How was it obtained?
  • Are there quasi-species?
42
Q

What is important to consider when using a recombinant virus?

A

Is it clonal or are there still variations?

43
Q

The dose of inoculum is generally much lower/higher than in humans?

A

Higher

44
Q

What are the options when choosing a route of inoculation? (8)

A
  • Intranasal
  • Intratracheal
  • Intraocular
  • Intravenous
  • Intra-oesophageal
  • Feeding
  • Contact
  • Aerosol
45
Q

Which route of inoculation is often used in transmission experiments?

A

Intranasal

46
Q

Which route of inoculation is often used to study viral replication?

A

Intratracheal

47
Q

Name model components related to methodology (2)

A
  • Frequency of monitoring
  • Time points
48
Q

What do you need to consider for time points?

A

Kinetics of disease in animal/human

49
Q

During the 2009 H1N1 outbreak, there was a need for which animal model?

A

Challenge model, that represented the disease as seen in humans

50
Q

What are the specific advantages of using ferrets as an animal model in influenza research? (5)

A
  • Receptor type and distribution similar to humans
  • Similar replication dynamics
  • Similar symptoms/clinical illness
  • Anatomy/histology: similar virus-associated pathological changes
  • Virus attachment similar
51
Q

Influenza: mice are not naturally susceptible to these viruses, how can these viruses be made mice specific?

A

Passaging the viruses in mice

52
Q

Which aspect of disease was studied in the H1N1 outbreak?

A

Diffuse alveolar damage (DAD)

53
Q

Why is intranasal inoculation not a good model to study DAD?

A

Causes high virus replication in URT, some in trachea/bronchi, but NO replication in lung/DAD

54
Q

Why is the cross reactivity of immune response between different H5 viruses very low?

A

Strongly varied antigenic responses

55
Q

Name three ways for respiratory virus transmission

A
  • Indirect contact
  • Direct contact
  • Airborne –> aerosol or droplets
56
Q

What is a good indication for whether new viruses are transmissible in humans?

A

Avian influenza viruses are usually not transmitted in ferrets

57
Q

What encompasses the EMC ferret transmission model?

A

Donor + direct contact –> indirect recipient

58
Q

What are characteristics of guinea pigs for influenza research? (4)

A
  • Less experience
  • Certainly different in pathogenesis
  • Easier to handle
  • Smaller
59
Q

Why are environmental chambers useful when studying viral transmission?

A

The effect of temperature and humidity on virus transmission efficiency can be studied

60
Q

Why may contact transmission between animals be a poor model for contact transmission between humans?

A

Animal behavior very different from humans

61
Q

Why may airborne transmission between animals be a better model for transmission between humans?

A

More realistic due to similar anatomy, behavior less of a concern

62
Q

For what purposes are transmission studies in animals useful to address fundamental questions in virology? (3)

A
  • Epidemiology
  • Climatic factors
  • Risk assessment

I&I SC2 (13 decks)

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