Lecture 32 Flashcards
What is HIV? How does it work? What can we do to help?
Human immunodeficiency virus, leads to acquired immune deficiency syndrome (AIDS) due to its infection of the immune system, which causes the immune system to fail.
The infected individuals will after a variable length of time progress to AIDS, leading to infections with pathogens, which will typically cause death. There are no cures or vaccines for this, there are new therapies with anti-retroviral drugs which can delay or possibly stop progression to AIDS, but it will not cure.
What do we find when we isolate the HIV genome? How can we find this genome?
HIV is a virus which often inserts its genome into infected human cells, using PCR we can isolate these viral genomes or pieces of it from infected patients. When we do this we find that not all HIV viruses have the same sequence (there is even variation of the virus within individuals), though the sequence is more closely related within a patient than between patients.
What is used to examine the relationship between HIV species? What do they show?
Phylogenetic trees are used for this, they trace the relationship between species, showing roughly when they diverged. We can create these from an alignment or DNA sequence using computers. Species with more of their sequence in common diverged more recently.
What can explain the pattern seen on a phylogenetic tree of HIV sequences? Give the evidence for and against each explanation. Which is more accepted?
The pattern is multiple sequences coming from each patient, these sequences are more closely related within a patient than between.
1. infection from multiple viruses: evidence for: Multiple sequences, suggesting infection from a bulk source of viruses
Evidence against: The pattern of the tree, if there were multiple infections why would viruses within a patient be more similar than between patients.
2. The viruses are changing (evolving) within a patient
For: Viruses within a patient are more similar than between, the pattern suggests a single point entry for a virus, followed by diversification.
Against: some patients have viruses from two parts of the tree.
2. is more accepted and it has been seen that new HIV viruses will emerge from a patient over time, proving the theory.
Why and how would HIV sequences change?
HIV is a lentivirus (type of retrovirus) and as such has an RNA genome and infects and damages immune cells. Having an RNA genome means it uses reverse transcriptase, a relatively error prone method to turn its RNA into DNA, these leads to lots of variants being formed. They may be selected for due to the immune system, drug regimens, changes in the receptor or tropism (growth) in particular tissues.
What parts of HIV make evolution easy for it?
RNA reverse transcriptase is very error prone, producing lots of mutations(variation), selection against HIV variants, A fast lifecycle means in the course of infection there is plenty of time for evolution, they also do undergo inheritance.
How can we test HIV’s evolution?
AIDs viruses from patients on anti-retrovirals have a different pattern of variation from that that are not. The most clear of these is the advent of resistant viruses (those resistant to treatment options).
What are the consequences of HIV’s rapid evolution?
Patients don’t have only one virus, they have many viral variants. Resistance to therapy, even complex therapy arises rapidly. Making effective vaccines is very hard.
What is a similar process to HIV’s rapid evolution which is also important in medicine?
Many pathogens can evolve within the host in the same way, hence why antibiotic resistance is spreading through bacterial populations. Our own genome evolves in response to pathogens but does so very slowly due to our longer life cycles.
