Evolution and medicine

Question 1

What is HIV?

Answer 1

• Lentivirus that causes aids
• Infections occurs through body fluids
• Causes the failture of the immune system

Question 2

What can delay HIV?

Answer 2

Antiretroviral drugs will delay or stop progression but will not cure

Question 3

How do we sequence the HIV virus?

Answer 3

Using PCR can isolate viral genomes, or pieces of viral genomes from infected patients (as the genome is often inserted into the human genome)

Question 4

What are phylogenetic trees?

Answer 4

They trace the relationships between species

- Differences in DNA sequence will show the relationships between species so we can draw a tree from this

Question 5

What did the tree of HIV sequences show?

Answer 5

That multiple sequences come from each patient

• These sequences are more closely related within a patient than between
• Different variants of the virus within one person

Question 6

What are the two proposed explanations for the HIV sequence tree?

Answer 6

1. Infections from multiple viruses
   - Each patient may have more than one viral sequence because they were infected with multiple viruses
2. Viruses are changing
   - The multiple sequences may be sue to the viruses changing within a patient

Question 7

What is the prediction from the virus changing hypothesis?

Answer 7

If the viruses are changing then if we sample a patient successfully then we should see different viral sequences appearing

Question 8

What does reverse transcriptase do?

Answer 8

Turns RNA into DNA

Question 9

How does reverse transcriptase produce a lot of variants?

Answer 9

It is very error prone - doesn’t repair its errors so a lot of variants arise due to this

Question 10

Can the variants in patients be explained by the mutations caused by reverse transcriptase?

Answer 10

No.. as do not find inactivating mutations; all variants found only encode for active working viruses

Question 11

What are the four things needed for natural selection?

Answer 11

Variation (individuals in a population vary from one another)

Inheritance (Parents pass on their traits to their offspring genetically)

Selection (some variations reproduce more than others)

Time

Question 12

How does selection apply to the HIV virus?

Answer 12

• The immune system (e.g. particular HIV viruses may not bind CD4 receptor as well as others)
• Drug regimen (drug blocking HIV, any that can survive this will be selected for)
• Changes in receptor
• Tropism in tissues

Question 13

How does time apply to the HIV virus (to do will natural selection)

Answer 13

HIV life cycle is very fast, so in the course of an infection there is plenty of time for evolution

Question 14

Does HIV evolve?

Answer 14

Yes

Question 15

What is the biggest selection pressure for HIV ?

Answer 15

Aids viruses from patients on antiretrovirals have a different pattern of variation from those that are not
- Drugs are the biggest selective pressure on HIV viruses

Question 16

What are the consequences of HIV evolution?

Answer 16

• The HIV genome is the fastest evolving thing we know of
• The viruses evolve in the specific patient in order to target them better
• Resistance rises rapidly (even to complex therapy)
• Making effective vaccines is incredibly hard (as they evolve to fast)

Question 17

How does evolution relate to medicine?

Answer 17

• Evolutionary thinking can help us understand and better respond to pathogens like HIV
• Evolution is a key way that pathogens respond to hosts and therapy