Lecture 33: Evolution and Medicine

Question 1

What is HIV?

Answer 1

• A Lentivirus that causes AIDS (acquired immune deficiency syndrome)
• Infection occurs through bodily fluids
• Before disease was recognised, it was occasionally spread through contaminated blood products
• Virus infects and causes the failure of the immune system

Question 2

Infected individuals, after a variable length of time, progress to AIDS leading to ______ with ______ and fungi.

Answer 2

• Infections

- Bacteria

Question 3

New therapies involve anti-retroviral drugs will delay, or even stop progression to AIDS, but….

Answer 3

• Will not cure

Question 4

Using PCR you can isolate and amplify viral genomes in HIV, or pieces of viral genomes from infected patients. You will find…

Answer 4

• There’s difference between patients and within patients in terms of their sequences (different nucleotides, missing sequences)

Question 5

Phylogenetic trees …

Answer 5

• Trace the relationships between species

- You can also do this with DNA sequences

Question 6

By using phylogenetic trees in HIV patients we can see that…this could be caused by…

Answer 6

• Multiple coding sequences are closer to each other within patients than other sequences in different patients
• Infection from multiple viruses (1)
• Viruses are changing (2)
  Patient 9, over a time period whole family of viruses appeared to have “dropped dead”
• The reason there is variation is because viruses are changing over time.

Question 7

Why does the HIV sequence change over time?

Answer 7

• Two explanations:
  How is the sequence changing?
  Why is the sequence changing?

Question 8

What is the mechanism by which the HIV sequence changes?

Answer 8

• HIV has an RNA genome (NOT DNA)
• HIV RNA genome reverse transcriptase-d into DNA
• There’s no way to tell whether there’s an error in this step
• Therefore lots of mutations
• Genome makes all the bits it needs to make a new virus
• Error checking when RNA back to DNA
• Mutation or evolution?

Question 9

All you need for natural selection is:

Answer 9

• Variation
• Inheritance : HIV genome pass on their traits to their offspring genetically
• Selection : any mutation that doesn’t work, dies
• Time : HIV lifecycle is very fast, so in the course of an infection there is plenty of time for evolution

Question 10

How can you test for HIV evolution?

Answer 10

• Change the selective pressure (virus evolves differently when you add retrovirals)
• AZT, now viruses are already resistant to it

Question 11

HIV patients don’t have a virus they have…

Answer 11

• A vast armada of viral variants

Question 12

The HIV Armada..

Answer 12

• Estimates of between 10^8 and 5 x 10^10 provirus containing cells in a patient
• Each one may be genetically distinct, can have up to 5 x 10^10 genetic variants

Question 13

Is HIV an isolated case?

Answer 13

• Even our own genome develops in this way

- Many other pathogens also use the same pathway