Flashcards in Lecture 28 - HIV vaccine? Deck (56)
How many people are currently infected with HIV?
How many people have died due to HIV?
Compare this to other things
Many more than world wars combined, Black death, Influenza outbreaks
How many people have been cured from HIV?
Berlin patient: seems to have largely cleared the virus
Atlanta baby: also seems to have cleared the virus
Describe the structure of HIV
- cone shaped
- envelope spikes
What is notable about enveloped viruses?
Labile in the environment
Describe the genome of HIV
Two copies of RNA genome
Covered by nucleocapsid
What is the CA capsid?
This is what makes up the icosahedral capsid of HIV
What proteins does HIV make?
1. gag: structural proteins
2. pol: enzymes (reverse transcriptase etc)
3. env: glycoproteins
Describe how HIV replicates
1. Surface glycoproteins
4. Reverse transcription
5. Insertion into host genome
6. Transcription and translation
Which cells does HIV infect?
Why these cells in particular?
CD4+ T cells
Virus surface proteins bind to CD4 protein
What is important about RT?
Very error prone
One mistake everytime the genome is reverse transcribed
What does 'Integrated provirus' mean?
It's genome is inserted into the host genome
What are the phases of HIV infection?
• Clinical latency
• Symptomatic disease
Describe primary infection
• Shortly after infection, lasts a few weeks
• High numbers of circulating virus
• Rapid loss of CD4+ in blood and lymph nodes
What happens during clinical latency?
• Virus continues to replicate
• Immune system keeps levels quite low
• Ongoing decline in CD4+ T cells
What happens after a number of years of clinical latency?
• Very few CD4+ left
• Immune system no longer able to control opportunistic infections
What are the yellow nodules seen in the gut?
Healthy Peyer's patches with lymphocytes
What happens to the GALT in HIV+ patients?
• 60% of T cells in GALT are lost within days
• Loss of tight junctions
• Decreased cytokine production
→ increased infection from the GIT
Describe the immune response to HIV in general
Initial: After primary infection, the immune response can contain the virus to a certain extent
An equilibrium is reached
Later: HIV escapes immune system
• Immune system depletion
What allows HIV to eventually avoid the immune response?
The rapid mutation due to RT
• antibodies can't recognise new clones
• CD8+ doesn't recognise either
Describe what happens once the HIV escapes the immune system
Loss of T cells
No help for
• B cells
Describe macrophage activity during HIV infection
• removal of pathogens
What sort of infections occur later on?
• Fungal infections
When do people start to feel sick with HIV infection?
After years of infection
What factors affect outcome of infection?
What are the targets of HIV antivirals?
• reverse transcriptase enzyme inhibitors
• protease inhibitors
• integrase inhibitors
• entry inhibitors
What sort of things kills HIV+ people nowadays?
Diseases as a result of chronic immune activation
• Liver disease
• Non-AIDS Cancers
• Heart disease
What is HAART?
Highly active anti-retroviral therapy
Many antivirals given
Less chance of resistance
Describe the efficacy of HAART
With use of HAART, HIV+ people increase their life span dramatically
Life expectancy only 10 less than HIV- people