Animal models: virology Flashcards
What is the definition of an ‘animal model’?
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
What are animal models historically known for?
For obtaining information on physiology and disease
What are animal models heavily regulated by? (3)
- Legislation
- Guidelines
- Experimental design requirements
What are the three R’s?
- Refine procedures (most humane way)
- Reduce the number of animals
- Replace with non-animal alternatives
Which guidelines can be used for reporting animal research?
ARRIVE
Which guidelines can be used for planning animal research?
GUIDE
What are important factors when choosing the correct animal model? (3)
- Consider research question
- Susceptibility, tissue (tropism), clinical signs
- Comparability human vs. animal
What are important factors to consider about the chosen animal model (6)?
- Age
- Sex
- Genetic background
- Microbiological status
- Comorbidities
- Variation
Name general influential factors and important aspects of animal models in virology (5)
- Acclimatization to new housing in animal facility
- Housing
- Biology and behavior of the animal model
- Containment level
- Sampling (which, when, how often)
Why is acclimatization to new housing in animal facility important?
Provides stress-free animals at the start of the experiment
Which clinical signs and clinical scores can be used to measure in animal models in virology? (4)
- Body weight
- Appearance
- Behaviour/activity
- Body temperature
What are ‘other’ factors to consider when choosing an animal model in virology? (3)
- Humane endpoints
- Anesthesia and euthanasia
- Post experimental analysis
What is important about anesthesia and euthanasia? (2)
- Should not interfere with read-outs
- Should not cause excessive discomfort
What factors should be considered about the reagents (vaccines, antivirals, etc)? (4)
- Adjuvant
- Concentration
- Route of administration
- Schedule
What factors do you need to consider when selecting the virus for the experiment? (6)
- Strain
- Origin and propagation of virus
- Which titer do you give to animals?
- Quality of virus
- Stability
- Alterations necessary?
Which animal model is often the first choice to study unknown human viruses?
Non-human primates (NHP)
Why do you always have to think of different ways to answer the question? (with respect to NHP)
NHP are very expensive and ethically questionable
Name River’s modified Koch’s postulates (6)
- 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
Why do you look into specific immune response to the virus in animals?
Confirms that agent causes the disease in animals
Name the common animal models for SARS-CoV (4)
- NHP
- Golden Syrian hamster
- Ferrets
- Transgenic mice
MERS-CoV: Why did ferrets not seroconvert after intranasal/intratracheal inoculation with high dose of virus?
Ferret DDP4 does not bind MERS-CoV
What can you do if there is no correct animal model?
Adaptation of virus to host by serial passaging in host of interest
Summary: name three important factors to consider when choosing an animal model for MERS-CoV experiments?
- 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
What are common animal models used for MERS-CoV experiments? (3) Which is most often used?
- Rabbits
- Healthy, young NHPs
- Transgenic mice with hDPP4 receptors (most often used)
