L36: Evolution and Medicine

• HIV-AIDS is passed on through bodily fluids
• HIV is a lentivirus that causes AIDS. There have been 25 million deaths between 1981 and 2006 because of this.
• before the disease was recognised, it was occasionally spread through contaminated blood products
• HIV affects 0.6% of the population, about 2.5% of deaths worldwide
• Virus infects and causes the failure of the immune system
• HIV is a virus and has a genome that is often inserted into the human genome infected cells
• Using PCR (amplification), you can isolate viral genomes, or pieces of viral genomes from infected patients. We are able to find closely related viruses
• Using Phylogenetic trees, we can see who is related and the virus cause
• Multiple sequences come from each patient. These sequences are much more related within a patient than between.
• Two types of sequence changes are proximate and ultimate
• proximate is by what mechanism is the change occuring
• ultimate is what is causing the change
• 1. infections from multiple viruses

  each patient may have more than one viral sequence because they were infected with mutliple viruses
• evidence for infections from multiple viruses have: multiple sequences and infection from a bulk source
• evidence against infections from multiple viruses is the pattern of the tree - if there were multiple infections, why are virsues within patients more similar
• 2. viruses are changing

  the multiple sequences may be due to the viruses changing within a patient
• evidence for viruses changing is viruses within a patient are more similar than between. the pattern of the tree suggests a single point of entry of a virus
• evidence against viruses are changing is patient 91 has a viruses in two parts of the tree
• prediction that viruses are changing is that if we see a patient successfully then we should see a different viral sequence appearing.
• what do we know about HIV that might change the mechanism by which its sequence changes?

  • HIV is lentivirus
  • has a RNA genome
  • infects and damages immune system cells
• reverse transcription is an enzyme that turns RNA sequence back into DNA. The HIV genome is RNA, but is turned into DNA to insert in the genome
• Reverse transcription is more error prone than DNA replication, so lots of variants are formed
• We do not find inactivating mutations; all variants found encode active, working viruses
• evolution is caused by natural selection
• requirements for natural selection

  1. variation - individuals in a population vary from one another
  2. inheritance - parents pass on their traits to their offspring
  3. selection - some variants reproduce more than others
  4. successful - variants accumulate over many generations
• HIV has variation, it is sorted by error-prone nature of HIV reverse transcription. It also has inheritance, HIV viruses pass on their RNA after being inserted in the genome
• HIV also has selection, the immune system, drug regimen, changes in the receptor and tropism. it also have time, the HIV lifecycle is very fast, so there is time fr evolution
• HIV evolves because AIDS viruses from patients on anti-retrovirals have a different pattern of variation from those that are not.
• HIV genome holds the record fro the fastest evolving thing we know of.
• Consequences of HIV evolving

  • patients don't have a virus, they have a vas armada of viral variants
  • resistance to therapy, even complex therapy arises rapidly
  • making effective vaccines is difficult.
• Many pathogens evolve within the host in the same way. The antibiotic resistance spreading through a population of bacteria is also evolutionary process. Even out own genome evolves in response to pathogens
• 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.