Flashcards from NOTES Exam 1 (Lindsay & Sam)
Why are the rates of HIV so high in Africa (even though the rates are starting to fall), and much lower in North America and other regions?
- -likely mode of transmission greatly differs between regions
- -ex: USA uses more condoms, so people are less likely to come in contact with bodily fluids
What is the mechanism of infections of HIV?
HIV infects T-cells
1) HIV specifically binds to CD4 receptor on T cell
2) Integrase promotes fusion of viral DNA and host DNA (Tcell)
3) Reverse Transcriptase transcribes viral DNA
4) Host T cell proliferates and thus makes copies of viral DNA within the host
5) Transcription and translation create HIV proteins and HIV RNA, leading to assembly of the new HIV virion which budds off
6) Budding off forms a mature virus that will go infect other T cells
How is HIV unlike other viruses in respect to its infection mode? Why is this?
- -Unlike other virus variants, HIV wants to “switch on immune” system so that it can keep infecting new T-cells
- -Why? Because it needs active T cells to proliferate
What is AZT? What does it do?
- -AZT was the first successful treatments (AZT Triphosphate)
- -AZT Therapy: antiviral treatment that takes advantage of reverse transcriptase
How does AZT take advantage of reverse transcriptase and thus work in fighting HIV?
- -Human enzymes don’t bind AZT triphosphate (so normal human transcriptase isn’t really affected by it), but RNA reverse transcriptase doesn’t sense AZT, and so it jams reverse transcriptase
- -(AZT doesn’t affect normal human transcriptase)
Why isn’t AZT a “cure” or solution to HIV?
- -Over time, higher concentrations of AZT were needed in order to see same effects, bc HIV virus was developing resistance
- -HIV is evolving
HIV shows varying susceptibility to AZT over time but gains resistance through evolution.
What are theories as to how it does this?
- -Reverse transcriptase becomes more selective, so it’s not incorporating AZT as much
- -This mutation can lead to natural selection as that virus is able to survive in the environment and pass on its DNA
What is HAART?
–hightly active anti-retroviral therapy (uses multiple anti-virals; early HAART refers to the time in development, not infection)
Why are some individuals more resistant to acquiring HIV virus?
- -The cofactor which allows for entry of virus gene is deleted in these people
- -Highest resistance to HIV in Baltic States (near Scandinavia)
- -(Lowest in Africa where HIV is highest)
What are the genotypes that determine how resistant an individual is to HIV in Africa?
- -Multiple variants of CD4 variants in africa
- -Genotype CC is at most reduced risk of infection
- -Genotype CT at least reduced risk
What is the trend of HIV gaining resistance within hosts? How does this help us trace the HIV evolution?
- -HIV evolves resistance within the hosts.
- -If patient aquires one strain over months to years, the individual has different variants without acquiring new strain from another infected individual.
- -In case where individual was intentionally infected, the original strain can be traced back using sequencing and evolutionary trees.
How did HIV become a contractible virus for humans?
–Origin of HIV stems from consumption of monkey meat, 3 separate infection events
What are the theories as to how HIV will evolve? What matters for the virus?
–Virus may evolve in a more benign direction–discounted because virus is being selected to increase viral load and infect more people
–In looking at patients, competitive fitness of virions increases with time, so virus increases their target selection and expands to naive Tcells
–Progression rate is correlated with rate of synonymous mutations
OVERALL: all that matters for the virus is the rate of duplication
