Immunology - HIV infection

Question 1

Using which enzyme does HIV replicate inside cells?

Answer 1

Reverse Transcriptase

Question 2

How many genes are inside the HIV genome?

Answer 2

9 genes that encode 15 proteins

Question 3

What is the role of reverse transcriptase in HIV?

Answer 3

Converts RNA into DNA which can be incorporated into host cells’ genes

Question 4

What are the two key glycoproteins encoded by the HIV virus?

Answer 4

gp120 (initial binding)
gp41( conformational change)

Question 5

Which cell of the immune system is particularly affected by HIV?

Answer 5

CD4+ T cells

Question 6

Recall the receptor and co-receptors for HIV on CD4+ T cells

Answer 6

CD4 receptors
CCR5 CXCR4 coreceptors

Question 7

In people who have natural immunity to HIV, what antibodies may be present in serum?

Answer 7

Anti-gp120 and anti-gp41 (Nt) antibodies

Question 8

How does HIV infection affect CD8+ T cells?

Answer 8

by affecting the function of CD4+ T-cells and antigen presenting cells that are required for proper CD8+ T-cell maturation, HIV is able to decrease the circulating pool of effector and memory CD8+ T-cells that are able to combat viral infection

Question 9

How does HIV infection affect monocytes and dendritic cells?

Answer 9

Not activated by CD4+ T cells and so cannot prime naive CD8+ T cells

Question 10

How does HIV affect immunological memory (2)?

Answer 10

CD4+ T cell memory is lost

CD8 memory cell not activated by antigen-presenting cell

Question 11

Why is there so much variation/mutation in HIV infection?

Answer 11

lacks proof-reading mechanisms from cellular DNA polymerases

Question 12

Why is HIV mutation within the host problematic (3)?

Answer 12

Escape from neutralising antibodies.

Escape from HIV-1-specific T cells.

Resistance and escape from antiretroviral drugs.

Question 13

Recall the 7 steps of the HIV life cycle

Answer 13

1. Attachment/Entry
2. Reverse Transcription and DNA Synthesis
3. Integration
4. Viral Transcription
5. Viral Protein Synthesis
6. Assembly of Virus and Release of Virus
7. Maturation

Question 14

Which drug classes are capable of inhibiting the action of reverse transcriptase in HIV infection?

Answer 14

1. Nucleoside analogues reverse transcriptase inhibitors
2. Non-nucleotide reverse transcriptases inhbitors

Question 15

Which class of HIV drugs can prevent integration of viral DNA?

Answer 15

Integrase inhibitors

Question 16

Which HIV drugs can prevent modification of translated viral proteins?

Answer 16

Protease inhibitors

Question 17

What is the median time of infection with HIV to AIDS development?

Answer 17

8-10 years

Question 18

What does it mean if someone is an HIV exposed seronegative individual?

Answer 18

Partner of individual with HIV who remains uninfected

Question 19

What are the 3 major markers used to monitor HIV?

Answer 19

CD8
CD4
Plasma viral load

Question 20

What is long-term nonprogression of HIV?

Answer 20

individuals who are infected with HIV, but control the infection without antiretroviral therapy (ART).

individuals who have been living with HIV for at least 7 to 12 years and have stable CD4+

Question 21

How can HIV be diagnosed (2)?

Answer 21

anti-HIV antibodies (ELISA) - screening test

Western Blot = Confirmatory test

Question 22

How are CD4+ T cell levels measured in HIV infection?

Answer 22

Flow cytometry

Question 23

What are the two methods of testing for ARV resistance?

Answer 23

Phenotypic = viral replication is measured in cell cultures under selective pressure of increasing concentrations of antiretroviral drugs (compared to wildtype)
Genotypic = mutations detected by sequencing amplified HIV genome (limited to sequencing RT and P)

Question 24

Which drugs make up a HAART regimen?

Answer 24

Three or more ART drugs

Question 25

When should HAART treatment be initiated?

Answer 25

Immediately on diagnosis

Question 26

Give 3 examples of NRTI HIV drugs

Answer 26

Zidovudine
Lamivudine

Emtricitabine

Question 27

Recall 2 examples of protease inhibitor HIV drugs

Answer 27

Indinavir
saquinavir

Question 28

What class of drugs are dolutegravir & raltegravir?

Answer 28

Integrase inhibitor

Question 29

Which drugs make up the HAART regimen initially?

Answer 29

2 NRTIs + PI

Question 30

What CD4 count defines AIDS?

Answer 30

<200 cells/ mm3

Question 31

Which drugs make up the atripla pill?

Answer 31

Emtricitabine + tenofovir + efavirenz

Question 32

Which ARV is best to use in pregnancy?

Answer 32

Zidovudine

Question 33

How can CD8+ T cells prevent HIV entry into cells?

Answer 33

Producing chemokines MIP-1A, MIP-1b and RANTES which block co receptors

Macrophage Inflammatory Protein-1 Alpha

Question 34

does HAART elimiate HIV from body?

Answer 34

no - there’s a reservoir in CD4+ T cells

Question 35

4 ways of preventing HIV spread?

Answer 35

Male circumcision (APCs in foreskin at a high density)

Condoms

PrEP (Truvada)

TasP (Treatment as Prevention – if on treatment, cannot transmit infection; i.e. U=U)

Question 36

what type of virus is HIV

Answer 36

HIV is a retrovirus, which means it carries single-stranded RNA

contains reverse transcriptase

Question 37

whats gag protein

Answer 37

major structural protein (of HIV-1

Question 38

what is the 1st line screeening test for HIV and what is the confirmational test

Answer 38

Anti-HIV antibodies (ELISA) – screening test

Anti-HIV antibodies (Western Blot) – confirmation test

Question 39

whats a non-neutralising atibody seen in the adpative immune response to HIV?

Answer 39

anti-p24

Question 40

what predits disease progression?

Answer 40

initial viral burdern (set point)

Question 41

who are rapid progressors & elite controllers?

Answer 41

Rapid progressors (10%) will take 2-3 years to develop AIDS (these are mainly seen in Africa)

Elite Controllers (EC) can suppress the viral replication

Question 42

what does a positive test require?

Answer 42

A positive test requires the patient to have SEROCONVERTED (i.e. started to produce Ab) This happens after ~10 weeks incubation period

Question 43

what type of drug is efiraverz? what effect does it have on amplodipine

Answer 43

non NRTI

also a P450 inducer

amlodipine wont work as well

Question 44

3 outcomes of HAART

Answer 44

increases CD4 T cell count

controls viral replication

improvement in host defences

Question 45

4 limitations of HAART

Answer 45

doesn’t eradicate latent HIV-1;

fails to restore HIV-specific T-cell responses;

high pill burden;

adherence;

threat of drug resistance

Question 46

other than T lymphocytes, what cell type is primarily infected by HIV?

Answer 46

macrophages

Question 47

a mutation in what cell surface receptor may confer immunity from HIV?

Answer 47

CCR5

HIV is made up of two main viral envelope proteins:

gp120 - This receptor is responsible for initial binding to CD4 and a co-receptor, such as the CCR5 receptor.

gp41 - Binding of gp120 exposes gp41.

gp41 then leads to fusion with the host cell membrane and viral entry into the cell.

Mutations in the CCR5 receptor confer immunity against HIV as the virus cannot enter cells to replicate.

Question 48

outline the effects on HIV on the immune system

Answer 48

activated infected CD4 helper T cells die/anergised

therefore monocytea and dendritic cells arent activated and cant prime naive CD8 T cell

CD8 T cell and B cell responses lost as a consequence

CD4 T cell memory also lost

CTLs kill infected monocytes and dendritic cells

Question 49

give an example of a NNRTI

Answer 49

efavirenz

Question 50

give an example of a fusion inhibitor

Answer 50

enfuviritide

Question 51

gve an example of an attachment inhibitor

Answer 51

maraviroc