Evolution & Medicine Flashcards
What is HIV?
A lentivirus that causes AIDS
Where does infection of HIV occur?
Through bodily fluids
How many deaths occurred between 1981 and 2006?
WHO estimates 25 million
What happened before the disease was recognised?
It was occasionally spread through contaminated blood products
How much of the population does HIV affect?
0.6%
How many deaths are as a result of HIV?
3.5% of deaths worldwide (5.7% in low income countries)
What does the HIV virus infecting cause?
Failure of the immune system
HIV is a virus and…
has a genome
What happens with the HIV genome?
It is often inserted into the human genome in infected cells
What can be done using PCR?
You can isolate viral genomes, or pieces of viral genomes, from infected patients
What can come from each patient with HIV?
Multiple sequences
What is shown on a phylogenetic tree of HIV patients?
The sequences are more closely related within a patient than between patients
What are the possible explanations of the patter of HIV genomes on a phylogenetic tree?
Infections from multiple viruses or the viruses are changing
What is meant by infections from multiple viruses?
Each patient may have more than one viral sequence because they were infected with multiple viruses
What is evidence for people having infections from multiple viruses?
Multiple sequences, infection from ‘bulk source’
What is evidence against people having infections from multiple viruses?
The pattern of the tree - of there were multiple infections, why are viruses within patients more similar than viruses between patients
What is meant by the viruses are changing?
The multiple sequences may be due to the viruses changing within a patient
What is evidence for the viruses changing?
Viruses within a patient are more similar than between. The pattern of the tree suggests a single point of entry of the virus and then diversification
What is evidence against the virus changing?
Patient 91 has virus in two parts of the tree
What is the prediction for the virus changing?
If the viruses are changing then if we sample a patient successively then we should see different viral sequences occurring
What are the two types of explanation for the HIV sequence changing?
Proximate - By what mechanism is the change occurring
Ultimate - What is causing the change
What is a lentivirus?
A sort of retrovirus
What type of genome does HIV have?
a RNA genome
What does HIV do?
Infect and damage immune system cells
What is reverse transcriptase?
An enzyme that turns RNA sequence back Ito NDA
HIV sequence is RNA, but …
it is turned into DNA to insert into the human genome
Reverse transcription is …
more error prone than DNA replication so lots of variants are formed
Is it just a mutation?
The key is we do not find inactivating mutations, all the variants found encode active, working viruses. So is it evolution?
What is required for natural selection?
Variation, inheritance, selection, time
How does HIV show variation?
By the error-prone nature of HIV reverse transcription
How does HIV show inheritance?
HIV viruses pass on their RNA after being inserted in the genome
How does HIV show selection?
The immune system, drug regimen, changes in the receptor and tropism in tissues for or against the HIV variants
How does HIV shoe time?
HIV lifecycle is very fast, so in the course of infection there is plenty of time for evolution
How can it be tested if HIV evolves?
Changing the selective pressure or seeing if viruses evolve differently of you put. patient on anti-retroviral drugs
What is seen when it is tested if HIV evolves?
AIDS viruses from patients on anti-retrovirals have a different pattern of variation from those that are not
What is the most clear example of HIV evolving?
The advent resistance of viruses - first to AZT, now to ripple therapy or HAART (high active retroviral therapy)
What does HIV hold the record for?
The fastest evolving thing we know of
What do patients have?
The don’t have a virus, they have a vast armada of viral variants
What arises rapidly?
Resistance to therapy, even complex therapy
What is made hard by the rapid evolving of HIV?
Making effective vaccines
How many provirus containing cells are in a HIV patient?
10^8 to 5x10^10
What may each provirus containing cell be?
Genetically distinct, so assuming 1 provirus/cell we have up to 5x10^10 variants
What do many pathogens do?
Evolve within the host in the same way as HIV
What is also an evolutionary process?
The antimicrobial resistance spreading through a population
What does our own genome evolve to?
In response to pathogens
What can evolutionary thinking do?
Help us understand and better respond to pathogens like HIV
Evolution is …
a key way that pathogens response to hosts and therapy
