Evoltuion and medicine

Question 1

What is HIV?

Answer 1

Lentivirus that causes AIDS
Infection occurs through bodily fluids
1981-2006 ~ 25million deaths
Infects and causes failure of the immune system (most people don’t die of the disease itself, they die because their immune system can’t fight off other viruses)

Question 2

How can we sequence HIV?

Answer 2

The genome of HIV is often inserted into the human genome in infected cells
Using PCR you can isolate viral genomes or pieces of viral genomes, from infected patients

Question 3

What explains the pattern of the HIV sequence: infection from multiple viruses?

Answer 3

Each patient may have more than one viral sequence because they were infected with multiple viruses
EVIDENCE FOR: multiple sequences, infection from ‘bulk source’
EVIDENCE AGAINST: pattern of the phylogenetic tree for HIV - viruses within patients more similar than viruses between patients

Question 4

What explains the pattern of the HIV sequence: the viruses are changing?

Answer 4

The multiple sequences may be due to the viruses changing within a patient
EVIDENCE FOR: viruses within a patient are more similar than between
EVIDENCE AGAINST: patients can have viruses in two different parts of the tree

Question 5

What do we know about HIV that might explain the mechanism by which its sequence changes?

Answer 5

HIV is a lentivirus
It has an RNA genome
Infects and damages immune system cells

Question 6

Does HIV evolve?

Answer 6

Yes
It has variation due to error-prone nature of reverse transcription
It has inheritance as HIV pass on their RNA after being inserted
It has selection as the immune system changes in the receptor and tropism in tissues select for or against HIV variants
It has time: the cycle is very fast (~20mins) so plenty of time to evolve

Question 7

What is reverse transcription?

Answer 7

Reverse transcriptase is an enzyme that turns RNA sequence back into DNA
The HIV genome is RNA but it turned into DNA to insert in genome
Reverse transcription is more error prone than DNA replication hence lots of variants arise

Question 8

How can we test to see if HIV evolves?

Answer 8

AIDS viruses from patients on anti-retrovirals have a different pattern of variation from those that are not proving evolution occurs

Question 9

Consequences of HIV evolving

Answer 9

Patients don’t have A virus, they have MANY viral variants
Resistance to therapy, even complex therapy, arises rapidly
Making effective vaccines is incredibly hard

Question 10

How does evolution relate to medicine?

Answer 10

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