Lesson 1: Evolution of HIV Flashcards
One of the fastest evolving organism on earth
Human Immunodeficiency Virus (HIV)
HIV infects what
- macrophage
- T cell
among the deadliest epidemics in human history
Acquired Immunodeficiency Syndrome (AIDS)
In 2019, WHO estimated that
__ million have died
~__ million have been infected
~__ million people currently living with AIDS
- 32.7
- 75.7
- 38
Body fluids that transmits HIV
- blood
- semen (cum)
- vaginal fluids
- breast milk
- pre-seminal fluid
- rectal fluids
Mode of Transmission:
Certain body fluids must come in contact with a __ or __ or be directly __ into the bloodstream (from a needle or syringe) for transmission to occur.
- mucous membrane
- damaged tissue
- injected
Mucous membranes are found inside the __, __, __, and __.
- rectum
- vagina
- penis
- mouth
Mode of transmission: High Risk
- Male-male sex
- Male-female sex
- sex work
- Pregnant woman (mother-to-child)
- Injection Drug use (sharing of injected needles)
Mode of Transmission: Little/No Risk
- Oral Sex, Biting, Spitting
- Food Contamination
- Deep, Open-Mouth Kissing
- Touching Tattoos
- Body Piercing
- Medical Care
any of a family of RNA viruses that have an enzyme (reverse transcriptase) capable of making a complementary DNA copy of the viral RNA, which then is integrated into a host cell’s DNA.
Retrovirus
HIV is a retrovirus with two single-strand __
RNA genomes
HIV uses the enzyme __ to replicate RNA → DNA
reverse transcriptase
HIV has an __ to incorporate its genome into the host genome
integrase
HIV Life Cycle:
1. As it comes up to the surface of helper T cell, it uses the __.
2. It binds to the envelope’s (HIV) proteins resulting in a __ that allows a second receptor, __ to grab hold of the envelope.
3. The stalk of the envelope proteins pierces through the bottom to start drawing the helper T cell’s and viral __ together. This results in the __.
- CD4 receptors
- conformational change
- Chemokine coreceptor (CCR5)
- membranes
- fusion of two membranes
HIV Life Cycle:
4. The viral __ is injected essentially into the helper T cell.
5. The __ is left at the cell’s surface
6. The virus has a __ and a __ which are essentially __ into the cell when it enters the cell, releasing the viral enzymes and viral RNA
7. Reverse transcriptase takes the __, using __, and converts that viral RNA into a single-stranded DNA. Both RNA strands
8. It makes __ and has a __–a characteristic of RT
- genetic material
- envelope protein
- matrix; capsid; digested
- viral RNA
- host nucleotides
- random errors
- poor proofreading ability
HIV Life Cycle
9. The __ grabs the double-stranded DNA and carries it through the __.
10. It finds its __ inside the nucleus. It makes a nick in the host DNA and allows HIV to insert itself into the host chromosome.
11. The __ makes __ and this encodes different viral proteins. It is associated with ribosomes on the surface of the rough endoplasmic reticulum.
12. The __ makes an envelope protein, which is directly produced into the endoplasmic reticulum. It is then taken to the __ and embedded into the __.
- integrase; nuclear pore
- host chromosome
- RNA Polymerase; mRNA
- mRNA; cell’s surface; cellular membrane
HIV Life Cycle:
13. Other __ also translate to other viral proteins (ex. Multi-protein chain). It is also transported to where the envelopes are and a strand of RNA, as well as some of the enzymes, are part of that complex.
14. That complex __ at the cell surface. It’s still not a mature virion because the __ needs to still be digested into its parts by an enzyme __ that allows them to coalesce and form the mature structures that make up the final infectious virion.
- mRNAs
- buds off
- polyproteins chain
- protease
Host Immune System vs HIV:
(a) __ capture the virus and present bits of its proteins to __. Once activated, these naive cells divide to produce __.
- Dendritic cells
- naive helper T cells
- effector helper T cells
Host Immune System vs HIV:
(b) __ stimulate __ displaying the same bits of viral protein to mature into __, which make antibodies that bind and in some cases inactivate the virus.
__ also help __, which destroy host cells infected with the virus
- Effector helper T cells
- B cells
- plasma cells
- Effector helper T cells
- killer T cells
Host Immune System vs HIV:
(c) Most effector T cells are short-lived, but a few become long-lived __.
memory helper T cells
What is the initial impact of HIV on the immune system?
HIV induces immune activation.
What is the consequence of immune system activation in response to HIV?
causes effector T-cell proliferation.
How does T-cell proliferation contribute to the progression of HIV infection?
gives HIV more target cells
Besides circulating in the bloodstream, where else does HIV specifically target CD4+ T cells?
CD4+ T cells in the gut
What are the long-term consequences of chronic infection and inflammation during HIV progression?
permanently damage lymph nodes and exhaust T-cell proliferation capacity, leading to diminished T-cell supply.
How does HIV impact CD4+ T cells in the gut, contributing to the progression of AIDS?
HIV infection depletes CD4+ T cells in the gut and damages gut tissues.
What happens when gut defenses are impaired during HIV infection?
Impaired gut defenses allow translocation of bacteria and their products from the gut into the bloodstream.
How might HIV evolve?
(1) Drugs impose Selection on HIV:
→ evolution of drug resistance
(2) Transmission Rate imposes Selection on HIV:
→ evolution of virulence
(3) Host immune system also imposes selection on HIV
a thymidine mimic which stops reverse transcription and impedes viral replication
AZT (Azidothymidine)
Why does AZT work initially but fail in the long run?
- fast mutation rate
- natural selection
Why does AZT work initially but fail in the long run?
■ FAST MUTATION RATE: Lots of mutations arise, including in the reverse transcriptase
gene of HIV → __
- genetic variation
Why does AZT work initially but fail in the long run?
NATURAL SELECTION favors __ that can recognize AZT and not use it (i.e., ones with the mutant now live, the others die)
reverse transcriptase enzyme mutant
The careful reverse transcriptase enzyme is __, but the virus is now resistant to AZT (__between fast & sloppy vs. slow & careful enzyme)
- slow
- evolutionary tradeoff
So, what would happen when AZT therapy stops?
Back mutations that restore the amino acid sequence to the original state are then favored by selection so that reverse transcription could __ again (fast & sloppy are favored – because fast replicating mutants would outgrow the slower ones).
- speed up
a situation in which evolution cannot advance one part of a biological system without distressing another part of it.
evolutionary trade off
Why does HIV need to strike an evolutionary tradeoff in terms of virulence?
HIV needs to keep the host alive long enough to be transmitted to the next host.
How does high transmission rate relate to virulence in HIV evolution?
High Transmission Rate is associated with High Virulence; faster viral growth is beneficial even if the host dies.
Explain the advantage of high virulence in HIV with a high transmission rate.
High virulence allows the virus to grow rapidly, increasing the chances of jumping to the next host. Strains with faster growth may outcompete others.
hat happens when the transmission rate is low in terms of virulence selection for HIV?
Low Transmission Rate is associated with Low Virulence; strains that are less virulent (don’t kill the host quickly) are favored.
High Transmission Rate: will select for __
High Virulence
Low Transmission Rate: will select for __
Low Virulence
What is a key strategy to combat HIV evolution towards more fatal strains?
Must lower transmission rate of HIV to discourage the evolution of more fatal strains.
What factors should be understood to combat HIV evolution?
Evolutionary properties of a disease, including:
- Evolutionary history
- Mutation rate
- Selective forces
- Evolutionary tradeoffs
How does HIV evolve in response to the antiretroviral drug AZT?
Evolution in response to AZT includes a tradeoff between slow and accurate replication versus fast and sloppy replication.
What is the evolutionary response to transmission rate in combating HIV?
Evolution in response to transmission rate involves a tradeoff between:
- Slow growing and less virulent (to keep the host alive)
- Fast growing and more virulent (for higher transmission)
What potential intervention is suggested to combat HIV evolution in the host?
Gene therapy
