Viral Evolution

Question 1

What is the origin of viruses?

Answer 1

The origin of viruses is still debated, but there are 3 main theories:
- Regressive evolution
- Escape hypothesis
- Virus-first hypothesis

Question 2

What is the regressive evolution?

Answer 2

The theory that viruses were once small cells that became parasitic and lost essential genes over time.

Question 3

What is a strength and weakness of the regressive evolution hypothesis?

Answer 3

Strength:
- Viruses mimic intracellular bacteria like Chlamydia
Weakness:
- Doesn’t explain viral hallmark genes (e.g. capsid proteins)

Question 4

What is the escape hypothesis?

Answer 4

The theory that viruses are mobile genetic elements (like transposons/plasmids) that “escaped and gained infectious capacity

Question 5

What is a strength and weakness of the escape hypothesis?

Answer 5

Strength:
- Similarities between viral replication genes & host mobile elements
Weakness:
- Fails to explain large viruses & hallmark genes

Question 6

What is the virus-first hypothesis?

Answer 6

The theory that viruses arose before cellular life- relics of a pre-cellular world

Question 7

What is a strength and a weakness of the virus-first hypothesis?

Answer 7

Strength:
- Explains hallmark genes
- Consistent with viruses infecting all domains of life
Weakness:
- Hard to prove directly
- Relies purely on models of early life

Question 8

Is retrovirus replication error prone?

Answer 8

Yes. The reverse transcriptase they use lacks proofreading (like RdRP), so is error prone

Question 9

What are the pros and cons of viral mutation?

Answer 9

Pros:
- Rapid adaptation
Cons:
- Risk of error catastrophe (lethal mutagenesis)

Question 10

In general, what are the main way RNA vs DNA viruses avoid immune response?

Answer 10

RNA viruses- mutational escape (antigen drift)

DNA viruses- latency, immune modulation

Question 11

How can lethal mutagenesis be used as an antiviral strategy?

Answer 11

• Increase viral mutation rates using nucleoside analogues
• Pushes virus beyond error threshold, so cannot produce a functional progeny (offspring)

Question 12

What are the requirements for effective mutagens (to cause lethal mutagenesis)?

Answer 12

• Efficient transport into host cells
• Conversion into triphosphate form
• Preferential incorporation by viral polymerase over host polymerase
• Must cause non-complementary base pairing

Question 13

What is an example of a nucleoside analogue mutagen?

Answer 13

AZT, which is used against retroviruses like HIV