Lecture 13 - HIV Epidmiology, Virology Flashcards
Number of people living with HIV currently
~35 million
Treatment coverage currently in Botswana
95%
Rate of HIV infection from injected drugs in Australia
Very low
From availability of clean needles
Proportion of Australian newly diagnosed HIV infections in men who have sex with men
~2/3
Most common method of HIV transmission world wide
Heterosexual contact (80 - 85%)
Behavioural and social factors leading to HIV epidemic 1) 2) 3) 4) 5) 6)
1) Little to no condom use
2) Multiple sexual partners
3) Overlapping sexual partners
4) Large sexual network
5) Age mixing
6) Women dependent on marriage or prostitution
Biological factors leading to HIC epidemic 1) 2) 3) 4)
1) Low level of male circumcision
2) High STI rates
3) HIV subtype
4) Host genetics
Family of viruses that HIV belongs to
Lentiviridae
Primate retrovirus closely related to HIV-2
SIVsm (Sooty Mangabey)
Primate retrovirus closely related to HIV-1
SIVcpz (Chimpanzee)
HIV size
80 - 130nM
HIV envelope
Envelope positive
HIV genome
Diploid, linear
10kb + sense ssRNA
Where is the HIV genome replicated?
Nucleus
Where is the HIV virus assembled?
Cytoplasm
Diseases caused by HIV
AIDS
Neurologic
Arthritis
Pneumonia
Components of a generic retroviral genome
gag
env
pol
Contents of gag genes
Structural proteins
Contents of env genes
Envelope proteins
Contents of pol genes
Viral enzymes
Examples of env proteins
gp120
gp41
gp120 funciton
Cell surface attachment
gp41 function
Membrane fusion domain
Examples of gag genes
p7
p17
p24
p17
MA matrix protein
p24
CA capsid protein
p7
NC nucleocapsid protein
MA matrix protein
p17
CA capsid protein
p24
NC nucleocapsid protein
p7
Examples of pol genes
p66
p32
p11
p66
Reverse transcriptase
Reverse transcriptase
p66
p32
IN integrase
IN integrase
p32
p11
Protease
Protease
p11
Importance of knowing about HIV clades
Can trace epidemiology
Vaccines must be clade-specific
Number of T cells activated at any one time
~5%
Effect of HIV infection in active T cells
Kills T cell
Effect of HIV infection in resting T cells
Latent in cell
Proportion infected with R5 viruses
~95%
Stages of HIV infection 1) 2) 3) 4) 5) 6) 7) 8) 9)
1) CD4 binding
2) Coreceptor (CCR5, CXCR4) binding
3) Fusion
4) Viral genome reverse transcription
5) Viral genome integration into host genome
6) Viral genome transcription and translation
7) Viral assembly
8) Budding
9) Maturation
Number of HIV particles produced in a host per day
~10 billion
Effect of HIV infection of monocytes/macrophages
Slow release of virus
R5 viruses
CCR5-tropic HIV virus
X4 viruses
CXCR4-tropic viruses
D/M viruses
CCR5 and CXCR4-tropic viruses
Effect of CCR5-tropic viruses
Cause less T cell death
More common
X4 viruses
Cause more T cell death
Emerge late in AIDS infection
Proportion of AIDS patients with X4 virus
50%
CCR5 mutation that may contribute to HIV immunity
CCR5 delta32
What is delta32?
CCR5 mutant. HIV gp120 can’t bind to it
32bp deletion in CCR5 gene.
No negative effect on immune function
Proportion of people of European descent with delta32
5-14%
1% are homozygous
Where is delta32 rare?
Latin America
Sub-Saharan Africa
MIddle, East Asia
APOBEC3G function
Detects foreign RNA, modifies it
Which protein in humans edits foreign RNA?
APOBEC3G
Where could HIV-infected monocytes be located?
1) Brain (glial cells)
2) Lungs (alveolar macrophages)
3) GIT
4) Bone-marrow monocyte precursors
Role of macrophages in propagating HIV infection
Chronically infected, can serve as a viral reservoir
Cells infected by HIV 1) 2) 3) 4) 5)
1) CD4+ T cells
2) Macrophages/monocytes
3) Thymocytes
4) Dendritic cells
5) CD34+ progenitor cells
HIV protein that inhibits APOBEC3G
vif
What does vif inhibit?
APOBEC3G
TRIM5alpha role
Blocks uncoating of viruses
Which human protein blocks viral uncoating?
TRIM5alpha
Which HIV feature inhibits TRIM5alpha?
Capsid
Tetherin function
Prevents virus leaving cell
Which human protein prevents virus leaving cell?
Tetherin
Which HIV protein inhibits tetherin?
vpu
What does vpu inhibit?
Tetherin
LEDGF function
Tethers HIV to host chromatin
How does HIV travel from mucosal surface to lymph node?
1)
2)
1) Taken up by dendritic cell
2) Dendritic cell takes HIV to lymph node, where HIV infects active and resting T cells
Is the antibody response to HIV very effective?
No
Immune response that controls HIV infection
CD8+ T cell
What do tat, vpu and nef do?
Downregulate MHC expression
Ways that HIV can avoid immune system
1) Mutation
2) Downregulating MHC presentation
3) Loss of effector cells
4) Latency
5) Reach privileged sites of viral replication
Privileged sites of viral replication
1)
2)
3)
1) Brain
2) Testes
3) GIT
