Lecture 13 - HIV Epidmiology, Virology Flashcards Preview

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1

Number of people living with HIV currently

~35 million

2

Treatment coverage currently in Botswana

95%

3

Rate of HIV infection from injected drugs in Australia

Very low
From availability of clean needles

4

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

~2/3

5

Most common method of HIV transmission world wide

Heterosexual contact (80 - 85%)

6

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

7

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

8

Family of viruses that HIV belongs to

Lentiviridae

9

Primate retrovirus closely related to HIV-2

SIVsm (Sooty Mangabey)

10

Primate retrovirus closely related to HIV-1

SIVcpz (Chimpanzee)

11

HIV size

80 - 130nM

12

HIV envelope

Envelope positive

13

HIV genome

Diploid, linear
10kb + sense ssRNA

14

Where is the HIV genome replicated?

Nucleus

15

Where is the HIV virus assembled?

Cytoplasm

16

Diseases caused by HIV

AIDS
Neurologic
Arthritis
Pneumonia

17

Components of a generic retroviral genome

gag
env
pol

18

Contents of gag genes

Structural proteins

19

Contents of env genes

Envelope proteins

20

Contents of pol genes

Viral enzymes

21

Examples of env proteins

gp120
gp41

22

gp120 funciton

Cell surface attachment

23

gp41 function

Membrane fusion domain

24

Examples of gag genes

p7
p17
p24

25

p17

MA matrix protein

26

p24

CA capsid protein

27

p7

NC nucleocapsid protein

28

MA matrix protein

p17

29

CA capsid protein

p24

30

NC nucleocapsid protein

p7

31

Examples of pol genes

p66
p32
p11

32

p66

Reverse transcriptase

33

Reverse transcriptase

p66

34

p32

IN integrase

35

IN integrase

p32

36

p11

Protease

37

Protease

p11

38

Importance of knowing about HIV clades

Can trace epidemiology
Vaccines must be clade-specific

39

Number of T cells activated at any one time

~5%

40

Effect of HIV infection in active T cells

Kills T cell

41

Effect of HIV infection in resting T cells

Latent in cell

42

Proportion infected with R5 viruses

~95%

43

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

44

Number of HIV particles produced in a host per day

~10 billion

45

Effect of HIV infection of monocytes/macrophages

Slow release of virus

46

R5 viruses

CCR5-tropic HIV virus

47

X4 viruses

CXCR4-tropic viruses

48

D/M viruses

CCR5 and CXCR4-tropic viruses

49

Effect of CCR5-tropic viruses

Cause less T cell death
More common

50

X4 viruses

Cause more T cell death
Emerge late in AIDS infection

51

Proportion of AIDS patients with X4 virus

50%

52

CCR5 mutation that may contribute to HIV immunity

CCR5 delta32

53

What is delta32?

CCR5 mutant. HIV gp120 can't bind to it
32bp deletion in CCR5 gene.
No negative effect on immune function

54

Proportion of people of European descent with delta32

5-14%
1% are homozygous

55

Where is delta32 rare?

Latin America
Sub-Saharan Africa
MIddle, East Asia

56

APOBEC3G function

Detects foreign RNA, modifies it

57

Which protein in humans edits foreign RNA?

APOBEC3G

58

Where could HIV-infected monocytes be located?

1) Brain (glial cells)
2) Lungs (alveolar macrophages)
3) GIT
4) Bone-marrow monocyte precursors

59

Role of macrophages in propagating HIV infection

Chronically infected, can serve as a viral reservoir

60

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

61

HIV protein that inhibits APOBEC3G

vif

62

What does vif inhibit?

APOBEC3G

63

TRIM5alpha role

Blocks uncoating of viruses

64

Which human protein blocks viral uncoating?

TRIM5alpha

65

Which HIV feature inhibits TRIM5alpha?

Capsid

66

Tetherin function

Prevents virus leaving cell

67

Which human protein prevents virus leaving cell?

Tetherin

68

Which HIV protein inhibits tetherin?

vpu

69

What does vpu inhibit?

Tetherin

70

LEDGF function

Tethers HIV to host chromatin

71

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

72

Is the antibody response to HIV very effective?

No

73

Immune response that controls HIV infection

CD8+ T cell

74

What do tat, vpu and nef do?

Downregulate MHC expression

75

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

76

Privileged sites of viral replication
1)
2)
3)

1) Brain
2) Testes
3) GIT