Organoids in virology
11 important questions on Organoids in virology
What is the core concept of animal studies. And why fewer animals?
- Refinement
- Reduction
- Replacement
- ethics
- economics
- efficacy
Why are animal models not ideal for virology?
- A single mutation in the virus can make a difference
- Also a change in the host makes a difference
So you can use cell line to get anwers on questions like: how does the virus infect, how does it migrate to secondary sites (use of immune cells) etc. What is a disadvantage of these cell lines?
- To model migration and the blood brain barrier, you need co-cultures.
- The cell lines originate from cancer cells => not physiological respons
- Accumulate mutations
- Higher grades + faster learning
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What kind of organoids can be used for virology?
- Airway => they already make airway epithelium- mucus and cilia are being formed.
- Respiratory tract
- Intestinal culture
- etc
What is the advantage of human intestinal epithelium?
Own stem cells in the crypt
Brain organoids. What can you do with it?
- Modeling embryonic development
- Integrating microglia (important for defense mechanisms in the brain)
Parechovirus A. Leads to fever, diarhia, headache. Are there different phenotypes?
- PeV-A3 (severe and rare, central nerve system involved)
- PeV-A1 (mild and common, respiratory and gastric infection)
So how do we investigate why the two phenotypes cause different immune responses?
- Put them in brain organoids => look a response
- One of them was causing a much stronger immune response than the other one
- It was not just immune response -> neurons died because of ..?
- Start mapping out the infection cycle.
You can make two types of models which ones? And what is the goal in the future?
- High fidelity model => systemic overlap with the truth
- Discrimination model => only mimics a certain features, resembles the truth
Goals is to go toward higher fidelity => for example the gut-brain axis organ-on-chip model
Name some facts about primary immunodeficiency (PID).
- 450+ are rare
- example: combined immunodeficiency; disturbed T and B cell development
- severe enteric viral infections
They wanted to find a drug for these patient. What did they do?
Different steps.
- Looking for drug repurposing
- They found remdesivir: binds to viral RNA polymerase to terminate RNA transcription
- Tested it in the patients
- Saw a lot of individual differences
- Made a pipeline to predict the outcome of the medicine
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