HIV

Question 1

How many people are globally living with HIV (2023 estimate)?

Answer 1

40 million

Question 2

How many deaths in 2023 due to AIDS?

Answer 2

630,000

Question 3

What are diseases that are associated with AIDS?

Answer 3

A huge variety, from candidiasis to lymphoma

Question 4

What kind of virus is HIV?

Answer 4

Retrovirus

Question 5

What are of the world is most affected by HIV?

Answer 5

Sub-Saharan Africa

Question 6

What is the general treatment for HIV?

Answer 6

Anti-retroviral therapy, which reduces the viral load to undetectable amounts

Question 7

What is U=U?

Answer 7

Undetectable = untransmittable. If the viral load of HIV is undetectable levels, it cannot be transmitted

Question 8

What is HAART?

Answer 8

Highly active anti-retrovirus therapy.
A combination therapy used to treat HIV- typically involves taking three or more antiretroviral drugs at the same time.
The different drugs target different stages of HIV replication

Question 9

What cells does HIV attack?

Answer 9

Primarily CD4+ T cells.
The virus can also infect macrophages and dendritic cells

Question 10

What is the progression of HIV?

Answer 10

1. Acute HIV (2-4 weeks)
2. Latent HIV (often 10 years or more without treatment)
3. Acquired immunodeficiency syndrome (AIDS)
4. Advanced HIV disease (AHD)- can be considered a part of AIDS, characterised by frequent and severe opportunistic infections

Question 11

How do you determine AIDS diagnosis?

Answer 11

When their CD4+ T cell count falls below 200 cells/mm^3

Question 12

What is the life cycle of HIV?

Answer 12

Attachment
Entry
Reverse Transcription
Integration
Replication
Assembly
Budding

Question 13

How does HIV bind to the CD4+ T cells?

Answer 13

• HIV uses its gp120 protein to bind to the CD4 receptor on the surface of CD4 cells
• Can also gain entry through co-receptors like CCR5

Question 14

What is the entry step of HIV life cycle?

Answer 14

HIV viral envelope fuses with the CD4 cell membrane- release if viral contents into cell

Question 15

What is the reverse transcription step of HIV life cycle?

Answer 15

HIV RNA is converted into DNA by reverse transcriptase.
Newly formed viral DNA is transported into cell’s nucleus

Question 16

What drugs can target the reverse transcription step?

Answer 16

Nucleoside reverse-transcriptase inhibitors (NRTIs) like tenofovir
Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) like efavirenz

Question 17

How does tenofovir inhibit HIV reverse transcription?

Answer 17

Acts as false nucleotides that mimic natural nucleosides, allowing incorporation into the growing viral DNA chain, stopping its extension

Question 18

How does efavirenz inhibit HIV reverse transcription?

Answer 18

Bind to site of reverse transcriptase, causing conformational change that inhibits its activity

Question 19

What is the integration step of HIV life cycle?

Answer 19

Viral DNA integrates into host genome through enzyme integrase- allows hijacking of host cell machinery

Question 20

What drug is used to target integration step of HIV life cycle?

Answer 20

Dolutegravir, which inhibits the activity of integrase

Question 21

What is the replication step of HIV life cycle?

Answer 21

The integrated visa DNA uses host machinery to produce new viral RNA and proteins

Question 22

What is the assembly step of HIV life cycle?

Answer 22

New formed viral RNA and proteins move to cell surface, where they assemble as immature HIV particles

Question 23

What is the budding step of HIV life cycle?

Answer 23

The immature HIV particles bud off from host cell, taking a piece of cell’s membrane with them

Question 24

What is the role of protease in budding?

Answer 24

After the immature HIV particles bud off, protease cleaves the newly synthesised polyproteins into their functional components

Question 25

What are the poly proteins that are cleaved by protease?

Answer 25

Gag and Gag-pol

Question 26

What does the cleavage allow for the formation of?

Answer 26

Fully mature and infectious viruses

Question 27

What drugs can be used to target the budding step?

Answer 27

Anti-proteases like darunavir

Question 28

What are host restriction factors?

Answer 28

Intrinsic immune proteins that attempt to block HIV

Question 29

Give 4 examples of anti-HIV restriction factors?

Answer 29

APOBEC3G Tetherin TRIM5 SAMHD

Question 30

What is the role of APOBEC3G?

Answer 30

It is a cytidine deaminase that hyper mutates HIV DNA during reverse transcription = non functional

Question 31

What is the HIV countermeasure to APOBEC3G?

Answer 31

Vif protein, which binds to APOBEC3G, targeting it for degradation

Question 32

What is the role of tetherin?

Answer 32

Tether budding virions to the cell membrane, preventing release

Question 33

What is the HIV countermeasure to tetherin?

Answer 33

Vpu protein, which down regulates tetherin and promotes its degradation

Question 34

What is the role of TRIM5?

Answer 34

Binds to HIV capsid, triggering premature disassembly

Question 35

What is the HIV countermeasure to TRIM5?

Answer 35

HIV-1 has evolved to evade human TRIM5 (however is still susceptible to rhesus monkey TRIM5)

Question 36

What is the role of SAMHD?

Answer 36

Depletes dNTPs in myeloid cells (like macrophages, dendritic cells etc), starving retroviruses (like HIV) of dNTPs

Question 37

What is the HIV countermeasure to SAMHD?

Answer 37

The vpx protein found in HIV-2 targets SAMHD for degradation. However, HIV-1 lacks vpx, hence why it infects myeloid cells poorly

Question 38

What is the concept of HIV latent reservoir?

Answer 38

HIV establishes a long-lived supply of latently infected CD4+ T-cells, invisible to immune clearance and ART

Question 39

Why can latent HIV infected cells be undetected by the immune system and ART?

Answer 39

There is a transcriptional silence, so no new viral RNA/proteins are produced: - Immune cells can't detect infection - ART only targets active replication steps

Question 40

Why is ART a lifelong treatment?

Answer 40

Because of this latent reservoir. Latently infected cells can survive for decades

Question 41

What is the "Shock and Kill" strategy for treating HIV?

Answer 41

- Reactive latent HIV with latency reversing agents (Shock) - Use ART alongside immune system to kill infected cells

Question 42

What is a problem with "Shock and Kill"?

Answer 42

- Not all latent viruses become reactivated

Question 43

What is the Block and Lock strategy?

Answer 43

Use of latency promoting agents to deepen latency permanently

Question 44

What is a provirus?

Answer 44

The viral DNA of HIV that has been integrated and will replicate alongside the host cell. Equivalent to prophage in bacteriophages