Lesson 1: Evolution of HIV Flashcards

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1
Q

One of the fastest evolving organism on earth

A

Human Immunodeficiency Virus (HIV)

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2
Q

HIV infects what

A
  • macrophage
  • T cell
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3
Q

among the deadliest epidemics in human history

A

Acquired Immunodeficiency Syndrome (AIDS)

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4
Q

In 2019, WHO estimated that
__ million have died
~__ million have been infected
~__ million people currently living with AIDS

A
  • 32.7
  • 75.7
  • 38
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5
Q

Body fluids that transmits HIV

A
  • blood
  • semen (cum)
  • vaginal fluids
  • breast milk
  • pre-seminal fluid
  • rectal fluids
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6
Q

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.

A
  • mucous membrane
  • damaged tissue
  • injected
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7
Q

Mucous membranes are found inside the __, __, __, and __.

A
  • rectum
  • vagina
  • penis
  • mouth
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8
Q

Mode of transmission: High Risk

A
  • Male-male sex
  • Male-female sex
  • sex work
  • Pregnant woman (mother-to-child)
  • Injection Drug use (sharing of injected needles)
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9
Q

Mode of Transmission: Little/No Risk

A
  • Oral Sex, Biting, Spitting
  • Food Contamination
  • Deep, Open-Mouth Kissing
  • Touching Tattoos
  • Body Piercing
  • Medical Care
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10
Q

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.

A

Retrovirus

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11
Q

HIV is a retrovirus with two single-strand __

A

RNA genomes

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12
Q

HIV uses the enzyme __ to replicate RNA → DNA

A

reverse transcriptase

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13
Q

HIV has an __ to incorporate its genome into the host genome

A

integrase

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14
Q

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 __.

A
  1. CD4 receptors
    • conformational change
    • Chemokine coreceptor (CCR5)
    • membranes
    • fusion of two membranes
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15
Q

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

A
  1. genetic material
  2. envelope protein
  3. matrix; capsid; digested
    • viral RNA
    • host nucleotides
    • random errors
    • poor proofreading ability
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16
Q

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 __.

A
  1. integrase; nuclear pore
  2. host chromosome
  3. RNA Polymerase; mRNA
  4. mRNA; cell’s surface; cellular membrane
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17
Q

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.

A
  1. mRNAs
    • buds off
    • polyproteins chain
    • protease
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18
Q

Host Immune System vs HIV:
(a) __ capture the virus and present bits of its proteins to __. Once activated, these naive cells divide to produce __.

A
  • Dendritic cells
  • naive helper T cells
  • effector helper T cells
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19
Q

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

A
  • Effector helper T cells
  • B cells
  • plasma cells
  • Effector helper T cells
  • killer T cells
20
Q

Host Immune System vs HIV:
(c) Most effector T cells are short-lived, but a few become long-lived __.

A

memory helper T cells

21
Q

What is the initial impact of HIV on the immune system?

A

HIV induces immune activation.

22
Q

What is the consequence of immune system activation in response to HIV?

A

causes effector T-cell proliferation.

23
Q

How does T-cell proliferation contribute to the progression of HIV infection?

A

gives HIV more target cells

24
Q

Besides circulating in the bloodstream, where else does HIV specifically target CD4+ T cells?

A

CD4+ T cells in the gut

25
Q

What are the long-term consequences of chronic infection and inflammation during HIV progression?

A

permanently damage lymph nodes and exhaust T-cell proliferation capacity, leading to diminished T-cell supply.

26
Q

How does HIV impact CD4+ T cells in the gut, contributing to the progression of AIDS?

A

HIV infection depletes CD4+ T cells in the gut and damages gut tissues.

27
Q

What happens when gut defenses are impaired during HIV infection?

A

Impaired gut defenses allow translocation of bacteria and their products from the gut into the bloodstream.

28
Q

How might HIV evolve?

A

(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

29
Q

a thymidine mimic which stops reverse transcription and impedes viral replication

A

AZT (Azidothymidine)

30
Q

Why does AZT work initially but fail in the long run?

A
  • fast mutation rate
  • natural selection
31
Q

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 → __

A
  • genetic variation
32
Q

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)

A

reverse transcriptase enzyme mutant

33
Q

The careful reverse transcriptase enzyme is __, but the virus is now resistant to AZT (__between fast & sloppy vs. slow & careful enzyme)

A
  • slow
  • evolutionary tradeoff
34
Q

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).

A
  • speed up
35
Q

a situation in which evolution cannot advance one part of a biological system without distressing another part of it.

A

evolutionary trade off

36
Q

Why does HIV need to strike an evolutionary tradeoff in terms of virulence?

A

HIV needs to keep the host alive long enough to be transmitted to the next host.

37
Q

How does high transmission rate relate to virulence in HIV evolution?

A

High Transmission Rate is associated with High Virulence; faster viral growth is beneficial even if the host dies.

38
Q

Explain the advantage of high virulence in HIV with a high transmission rate.

A

High virulence allows the virus to grow rapidly, increasing the chances of jumping to the next host. Strains with faster growth may outcompete others.

39
Q

hat happens when the transmission rate is low in terms of virulence selection for HIV?

A

Low Transmission Rate is associated with Low Virulence; strains that are less virulent (don’t kill the host quickly) are favored.

40
Q

High Transmission Rate: will select for __

A

High Virulence

41
Q

Low Transmission Rate: will select for __

A

Low Virulence

42
Q

What is a key strategy to combat HIV evolution towards more fatal strains?

A

Must lower transmission rate of HIV to discourage the evolution of more fatal strains.

43
Q

What factors should be understood to combat HIV evolution?

A

Evolutionary properties of a disease, including:
- Evolutionary history
- Mutation rate
- Selective forces
- Evolutionary tradeoffs

44
Q

How does HIV evolve in response to the antiretroviral drug AZT?

A

Evolution in response to AZT includes a tradeoff between slow and accurate replication versus fast and sloppy replication.

45
Q

What is the evolutionary response to transmission rate in combating HIV?

A

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)
46
Q

What potential intervention is suggested to combat HIV evolution in the host?

A

Gene therapy