HIV Flashcards
How many people are infected with HIV and how many deaths each year
37 million affected
1.8 million new infections each years
1 million die
New infections fallen by 11% since 2011
What are the 4 types of HIV
HIV M, N, O, P
HIV M, N, O and are from Chimps, HIV P Is from gorillas
What did HIV N Cause
Only caused 13 infections
What did HIV O Cause
Circa 1920, caused tens of thousands of infections
How many subtypes of HIV 1 and HIV 2 are there
HIV 1 - 9 subtypes
HIV - 2 8 subtypes
Describe the genome organisation fo HIV
9700 nucleotides long
LTR at each end which are important for replication
Describe the HIV Genes
GAG: Capsid, Nucelopcapsid, Matrix
Pol: Reverse transcriptaes, Integrase, Protease
Env: Envelope glycoproteins GP120 and GP41
What are the regulatory auxillary proteins
Tat - stimulates processive transcription
Rev - binds RRE and facilitates nuclear export of unspliced or singly spliced RNA
What are the accessory auxillary proteins
Nef - can decrase expression of MHC, CD4 and CD8 receprots
Vif - antagonist of cellular protein APOBEC3G
Vpu - can cause G2 arrest –> facilitating entry of the pre-integration complex
Vpu - affects viral release as can disrupt the Env-CD4 complex
What is the target of nAB in HIV
The envelope glycoprotein is the only target
What is the structure of the envelope gylcoprotein
It is trimer of heterodimers of gp120 and gp41
What is involved in the reverse transcriptase complex
2xssRNA genomes tRNA primers viral protease reverse transcriptase protease
What is involved in the pre-integration complex
dsDNA Protease Integrase reverse transcriptase Matrix proteins Vpr
What are some key factors for integration
Emerin
Lens-Derived Epithelium Growth Factor (LDECF)
Barrier to autointegration factor (BAF)
What binds to HIV when latent
Nf-kB, HDACI and p50
In the active state how is HIV activated
Stimulation, i.e. TNF, induces the removal of HDACI and p50
Replaced with CBP/p300 –> causes acetylation
Tat interacts with the pTEFb complex –> comprised of CDK9 and cyclin T1 –> this recruits the stem loop structure TAR which acts as a promoter element in the viral LTR leading to production of full length transcripts
What cells does HIV infect
Infects cells of mucosal and cutaneous immune system
M cells - bowel epithelium
Dendritic cells - cervical and vaginal epithelium
Activated T Cells - genital sores, particularly HSV2
what is the major site of initial HIV infection
The GALT
What are the proposed mechanisms of CD4+ T Cell depletion
Direct killing by HIV (Fas mediated apoptosis, VPr induced apoptosis of G2 arrest, disruption of cell membrane integrity, accumulations of unintegrated DNA, integration of the provirus)
Killing of infected cells by HIV-1 specific CD8+ T cells
Extensive bystander immune activation
Antibody mediated cellular toxicity
What are the consequence of persistent immune activation
Increased cell turover
Skewign lymphoctes
Induction of cellular exhaustion, sensecence and low renewal potential
The regenerative capacity is progessively lost
Describe the characteristics of the children with HIV who were ‘elite controllers’
Low expression of CCR5
Low frequency of PD1+ T Cells
Low immune activation even with high l evels of viral replication
What mechanisms contribute to persistent
1) Regulation of gene expression –> i.e. acetylation at HIV promoter and chromatin remodelling etc
2) Immune activation –> periodic activation of target cells, upregulation of molecules modulating T cell survival e.g. PD1, decreased ability of immune system to recognise and destroy HIV infected cells
3) Specific HIV infected T cell subsets may be important
4) Pathways promoting lifelong memory may promote persistent infection
5) Cellular and tissue sources of persistence
Strategies to elimnate persistently affected cells
1) Deliberate infuction of viral gene expression
2) Recognising surface antigens on infected cells and targeted cell destruction
3) develop therapeutic vaccine to enhance immune mediated clearance of cells
4) Antibody production to control cell-cell virus transmission
5) Immune based therapeutics to reduce chronic immune activation
What is CD32a
Recently discovered on D4+ T cells harbouring latent HIV genomes
It is a receptor for IgG Fc
It is not present on normal CD4+ cells, but is on monocytes and platelts
THIS COULD BE A POTENTIAL TARGET TO DESTROY LATENTLY INFECTED CELLS! But it may only mark cells circulating in the blood
