HIV pathogenesis

Question 1

What makes up Gag (HIV)

Answer 1

p17 matrix antigen
p24 capsid antigen
p6/7 nucleocapsid

Question 2

What is HIV Pol made up of

Answer 2

Reverse transcriptase
Protease
Integrase

Question 3

What is HIV Env made up of

Answer 3

Surface glycoprotein (gp120)
Transmembrane glycoprotein (gp41)

Question 4

How many ORFs does HIV have?

Answer 4

Over 10

Question 5

Difference between HIV-1 and HIV-2 genomes?

Answer 5

Vpu in HIV-1 and Vpx in HIV-2

Question 6

Define viraemia

Answer 6

Virus in blood amount

Question 7

What rises to dampen the HIV infection?

Answer 7

HIV-specific CTL and anti-p24 Ab which then slowly fall

Question 8

What’s the set point in a HIV infection?

Answer 8

Lowest amount of viraemia after primary phase

Question 9

The lower the set point the longer the __________.

Answer 9

Asymptomatic phase

Question 10

What type of latency does HIV have?

Answer 10

Clinical latency

Question 11

What occurs during clinical latency

Answer 11

• 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.

Question 12

Clinical aspects of primary HIV infection:
M____-like syndrome
F____
M_____
R_____
D_____
L____

Answer 12

Mononucleosis-like syndrome
Fever
Malaise
Rash
Diarrhoea
Lymphadenopathy

Question 13

Clunical aspecs of clinical latency of HIV

Answer 13

No symptoms, sometimes fatigure, weight loss, thrush and shingles

Question 14

Normal levels of CD4 cells

Answer 14

2000/uL

Question 15

Complications when 200-500 CD4 cell/uL

Answer 15

Generalised lymphadenophy
Oral lesions esp candidiasis

Question 16

What viruses can reactivate/infect when 200-500 CD4/uL

Answer 16

Herpes zoster
Latent TB
Pxvirus
Papillomavirus

Question 17

HIV infected patients have more severe infections with DNA viruses or RNA viruses?

Answer 17

DNA viruses

Question 18

Protozal infections when CD4 levels are below 200

Answer 18

Toxoplasma gondii
Cryptosporidia
Microsporidia

Question 19

Bacterial infections when CD4 levels are below 200

Answer 19

Treponema pallidum, Mycobacterium avium intracellulare

Question 20

Fungal infections when CD4 levels are below 200

Answer 20

C. albicans and Cryptococcus neoformans

Question 21

Viral infections when CD4 levels are below 200

Answer 21

CMV
HSV
EBV lymphoma
KSHV
HPV

Question 22

What is AIDS dementia complex (ADC)

Answer 22

Infection of brain macrophages and glial cells

Question 23

How many AIDS patients have ADC

Answer 23

2/3

Question 24

Does HIV cause weight gain or loss

Answer 24

Loss due to blunting of intestinal villae, caused by rozix effects of viral proteins and indirect effects on cytokine regulation

Question 25

Why does HIV have pathogenic effects in the lungs?

Answer 25

Replication in lung macrophages

Question 26

What cell type does HIV infect

Answer 26

CD4+ Th cells

Question 27

Examples of CD4+ cells

Answer 27

Monocytes (precursors to APCs), macrophages, DCs

Question 28

How does HIV enter cells?

Answer 28

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

Question 29

Normal function of CD4

Answer 29

Binds Class II MHC on APCs and binds IL16

Question 30

Normal function of chemokine receptors?

Answer 30

Bind chemokines

Question 31

Structure of CD4

Answer 31

Four EC IgG like domains

Question 32

Structure of chemokine receptor

Answer 32

7 TM helices

Question 33

CxC is what type of chemokine receptor

Answer 33

Alpha

Question 34

CC is what type of chemokine receptor

Answer 34

Beta

Question 35

What does V3 loop also bind apart from chemokine receptor?

Answer 35

Heparan sulphate pripr to CD4/CCR5 binding

Question 36

What are two groups of HIV isolates?

Answer 36

R5 and X4 viruses

Question 37

What chemokine receptor do R5 viruses use

Answer 37

CCR5

Question 38

Are R5 viruses early or late in infection

Answer 38

Early

Question 39

Do R5 viruses fuse cells or not

Answer 39

Non-syncytium inducing (NSI) --> don't fuse cells

Question 40

Where do R5 viruses replicate?

Answer 40

Primary T-cells and macrophages, but not transformed T-cells

Question 41

What receptor do X4 viruses use?

Answer 41

CXCR4

Question 42

Are X4 viruses in early or late infection

Answer 42

Late

Question 43

Where can X4 viruses replicate?

Answer 43

Transformed T-cells and fuse cells (SI)

Question 44

What mutation do X4 viruses have?

Answer 44

V3 loop of gp120

Question 45

What differentiates R5 and X4 viruses?

Answer 45

V3 loop

Question 46

R5 viruses is _-tropic

Answer 46

M

Question 47

X4 virus is _-tropic

Answer 47

T

Question 48

Exposed but unifected indivudals have a deletion in what gene and which gene remains intact

Answer 48

CCR5 but intact CxCR4

Question 49

What is the port of entry for HIV

Answer 49

Macrophages in urogenital/anal mucosa

Question 50

Where is CCR5 highly expressed

Answer 50

Urogenital/anal mucosa

Question 51

What is the role of DCs in HIV infection

Answer 51

iDC as they mature, HIV associates with them and is transmitted into lymph node during maturation

Question 52

What does DC-SIGN usually bind

Answer 52

ICAM-3 on T-cell surface

Question 53

What binds to HIV envelope glycoprotein

Answer 53

DC-SIGN

Question 54

How does HIV get from DC to T-cell

Answer 54

Virological synapse, HIV moves along spindles from MTOC