Lecture 13 - HIV Epidmiology, Virology Flashcards by Jack Cuthbertson

Number of people living with HIV currently

~35 million

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Treatment coverage currently in Botswana

95%

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Rate of HIV infection from injected drugs in Australia

Very low

From availability of clean needles

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Proportion of Australian newly diagnosed HIV infections in men who have sex with men

~2/3

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Most common method of HIV transmission world wide

Heterosexual contact (80 - 85%)

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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

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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

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Family of viruses that HIV belongs to

Lentiviridae

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Primate retrovirus closely related to HIV-2

SIVsm (Sooty Mangabey)

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Primate retrovirus closely related to HIV-1

SIVcpz (Chimpanzee)

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HIV size

80 - 130nM

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HIV envelope

Envelope positive

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HIV genome

Diploid, linear

10kb + sense ssRNA

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Where is the HIV genome replicated?

Nucleus

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Where is the HIV virus assembled?

Cytoplasm

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Diseases caused by HIV

AIDS
Neurologic
Arthritis
Pneumonia

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Components of a generic retroviral genome

gag
env
pol

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Contents of gag genes

Structural proteins

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Contents of env genes

Envelope proteins

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Contents of pol genes

Viral enzymes

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Examples of env proteins

gp120

gp41

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gp120 funciton

Cell surface attachment

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gp41 function

Membrane fusion domain

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Examples of gag genes

p7
p17
p24

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p17

MA matrix protein

p24

CA capsid protein

NC nucleocapsid protein

MA matrix protein

p17

CA capsid protein

p24

NC nucleocapsid protein

Examples of pol genes

p66 p32 p11

p66

Reverse transcriptase

p66

p32

IN integrase

p32

p11

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?

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

Lecture 13 - HIV Epidmiology, Virology Flashcards

(76 cards)