HIV Flashcards
How many people are globally living with HIV (2023 estimate)?
40 million
How many deaths in 2023 due to AIDS?
630,000
What are diseases that are associated with AIDS?
A huge variety, from candidiasis to lymphoma
What kind of virus is HIV?
Retrovirus
What are of the world is most affected by HIV?
Sub-Saharan Africa
What is the general treatment for HIV?
Anti-retroviral therapy, which reduces the viral load to undetectable amounts
What is U=U?
Undetectable = untransmittable. If the viral load of HIV is undetectable levels, it cannot be transmitted
What is HAART?
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
What cells does HIV attack?
Primarily CD4+ T cells.
The virus can also infect macrophages and dendritic cells
What is the progression of HIV?
- Acute HIV (2-4 weeks)
- Latent HIV (often 10 years or more without treatment)
- Acquired immunodeficiency syndrome (AIDS)
- Advanced HIV disease (AHD)- can be considered a part of AIDS, characterised by frequent and severe opportunistic infections
How do you determine AIDS diagnosis?
When their CD4+ T cell count falls below 200 cells/mm^3
What is the life cycle of HIV?
Attachment
Entry
Reverse Transcription
Integration
Replication
Assembly
Budding
How does HIV bind to the CD4+ T cells?
- 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
What is the entry step of HIV life cycle?
HIV viral envelope fuses with the CD4 cell membrane- release if viral contents into cell
What is the reverse transcription step of HIV life cycle?
HIV RNA is converted into DNA by reverse transcriptase.
Newly formed viral DNA is transported into cell’s nucleus
What drugs can target the reverse transcription step?
Nucleoside reverse-transcriptase inhibitors (NRTIs) like tenofovir
Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) like efavirenz
How does tenofovir inhibit HIV reverse transcription?
Acts as false nucleotides that mimic natural nucleosides, allowing incorporation into the growing viral DNA chain, stopping its extension
How does efavirenz inhibit HIV reverse transcription?
Bind to site of reverse transcriptase, causing conformational change that inhibits its activity
What is the integration step of HIV life cycle?
Viral DNA integrates into host genome through enzyme integrase- allows hijacking of host cell machinery
What drug is used to target integration step of HIV life cycle?
Dolutegravir, which inhibits the activity of integrase
What is the replication step of HIV life cycle?
The integrated visa DNA uses host machinery to produce new viral RNA and proteins
What is the assembly step of HIV life cycle?
New formed viral RNA and proteins move to cell surface, where they assemble as immature HIV particles
What is the budding step of HIV life cycle?
The immature HIV particles bud off from host cell, taking a piece of cell’s membrane with them
What is the role of protease in budding?
After the immature HIV particles bud off, protease cleaves the newly synthesised polyproteins into their functional components
What are the poly proteins that are cleaved by protease?
Gag and Gag-pol
What does the cleavage allow for the formation of?
Fully mature and infectious viruses
What drugs can be used to target the budding step?
Anti-proteases like darunavir
What are host restriction factors?
Intrinsic immune proteins that attempt to block HIV
Give 4 examples of anti-HIV restriction factors?
APOBEC3G
Tetherin
TRIM5
SAMHD
What is the role of APOBEC3G?
It is a cytidine deaminase that hyper mutates HIV DNA during reverse transcription = non functional
What is the HIV countermeasure to APOBEC3G?
Vif protein, which binds to APOBEC3G, targeting it for degradation
What is the role of tetherin?
Tether budding virions to the cell membrane, preventing release
What is the HIV countermeasure to tetherin?
Vpu protein, which down regulates tetherin and promotes its degradation
What is the role of TRIM5?
Binds to HIV capsid, triggering premature disassembly
What is the HIV countermeasure to TRIM5?
HIV-1 has evolved to evade human TRIM5 (however is still susceptible to rhesus monkey TRIM5)
What is the role of SAMHD?
Depletes dNTPs in myeloid cells (like macrophages, dendritic cells etc), starving retroviruses (like HIV) of dNTPs
What is the HIV countermeasure to SAMHD?
The vpx protein found in HIV-2 targets SAMHD for degradation.
However, HIV-1 lacks vpx, hence why it infects myeloid cells poorly
What is the concept of HIV latent reservoir?
HIV establishes a long-lived supply of latently infected CD4+ T-cells, invisible to immune clearance and ART
Why can latent HIV infected cells be undetected by the immune system and ART?
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
Why is ART a lifelong treatment?
Because of this latent reservoir. Latently infected cells can survive for decades
What is the “Shock and Kill” strategy for treating HIV?
- Reactive latent HIV with latency reversing agents (Shock)
- Use ART alongside immune system to kill infected cells
What is a problem with “Shock and Kill”?
- Not all latent viruses become reactivated
What is the Block and Lock strategy?
