HIV pathogenesis Flashcards
What makes up Gag (HIV)
p17 matrix antigen
p24 capsid antigen
p6/7 nucleocapsid
What is HIV Pol made up of
Reverse transcriptase
Protease
Integrase
What is HIV Env made up of
Surface glycoprotein (gp120)
Transmembrane glycoprotein (gp41)
How many ORFs does HIV have?
Over 10
Difference between HIV-1 and HIV-2 genomes?
Vpu in HIV-1 and Vpx in HIV-2
Define viraemia
Virus in blood amount
What rises to dampen the HIV infection?
HIV-specific CTL and anti-p24 Ab which then slowly fall
What’s the set point in a HIV infection?
Lowest amount of viraemia after primary phase
The lower the set point the longer the __________.
Asymptomatic phase
What type of latency does HIV have?
Clinical latency
What occurs during clinical latency
- More CD4 cells killed than produced
- Lymph node destruction interferes with immune response
- Loss of CD4 cell function before depletion
- Accumulation of viral variants overwhelms the weakened immune system.
Clinical aspects of primary HIV infection:
M____-like syndrome
F____
M_____
R_____
D_____
L____
Mononucleosis-like syndrome
Fever
Malaise
Rash
Diarrhoea
Lymphadenopathy
Clunical aspecs of clinical latency of HIV
No symptoms, sometimes fatigure, weight loss, thrush and shingles
Normal levels of CD4 cells
2000/uL
Complications when 200-500 CD4 cell/uL
Generalised lymphadenophy
Oral lesions esp candidiasis
What viruses can reactivate/infect when 200-500 CD4/uL
Herpes zoster
Latent TB
Pxvirus
Papillomavirus
HIV infected patients have more severe infections with DNA viruses or RNA viruses?
DNA viruses
Protozal infections when CD4 levels are below 200
Toxoplasma gondii
Cryptosporidia
Microsporidia
Bacterial infections when CD4 levels are below 200
Treponema pallidum, Mycobacterium avium intracellulare
Fungal infections when CD4 levels are below 200
C. albicans and Cryptococcus neoformans
Viral infections when CD4 levels are below 200
CMV
HSV
EBV lymphoma
KSHV
HPV
What is AIDS dementia complex (ADC)
Infection of brain macrophages and glial cells
How many AIDS patients have ADC
2/3
Does HIV cause weight gain or loss
Loss due to blunting of intestinal villae, caused by rozix effects of viral proteins and indirect effects on cytokine regulation
Why does HIV have pathogenic effects in the lungs?
Replication in lung macrophages
What cell type does HIV infect
CD4+ Th cells
Examples of CD4+ cells
Monocytes (precursors to APCs), macrophages, DCs
How does HIV enter cells?
Interaction between gp120 and cell surface glycoprotein CD4
Conformational change in gp120 allows binding to co-receptor
gp41 conformational change exposes fusion domain
fusion between viral and cellular membranes allows entry of viral core
Normal function of CD4
Binds Class II MHC on APCs and binds IL16
Normal function of chemokine receptors?
Bind chemokines
Structure of CD4
Four EC IgG like domains
Structure of chemokine receptor
7 TM helices
CxC is what type of chemokine receptor
Alpha
CC is what type of chemokine receptor
Beta
What does V3 loop also bind apart from chemokine receptor?
Heparan sulphate pripr to CD4/CCR5 binding
What are two groups of HIV isolates?
R5 and X4 viruses
What chemokine receptor do R5 viruses use
CCR5
Are R5 viruses early or late in infection
Early
Do R5 viruses fuse cells or not
Non-syncytium inducing (NSI) –> don’t fuse cells
Where do R5 viruses replicate?
Primary T-cells and macrophages, but not transformed T-cells
What receptor do X4 viruses use?
CXCR4
Are X4 viruses in early or late infection
Late
Where can X4 viruses replicate?
Transformed T-cells and fuse cells (SI)
What mutation do X4 viruses have?
V3 loop of gp120
What differentiates R5 and X4 viruses?
V3 loop
R5 viruses is _-tropic
M
X4 virus is _-tropic
T
Exposed but unifected indivudals have a deletion in what gene and which gene remains intact
CCR5 but intact CxCR4
What is the port of entry for HIV
Macrophages in urogenital/anal mucosa
Where is CCR5 highly expressed
Urogenital/anal mucosa
What is the role of DCs in HIV infection
iDC as they mature, HIV associates with them and is transmitted into lymph node during maturation
What does DC-SIGN usually bind
ICAM-3 on T-cell surface
What binds to HIV envelope glycoprotein
DC-SIGN
How does HIV get from DC to T-cell
Virological synapse, HIV moves along spindles from MTOC
