L09: HIV Mutations

Question 1

Why are RNA viruses more prone to mutation than DNA viruses

Answer 1

RNA viruses get transcribed by RNA polymerase which do not point read and this leads to point mutations occuring.
DNA viruses are transcribed by DNA polymerase which proofread.

Question 2

What is an acute infection

Answer 2

Immune responce may clear individual viruses by variations can re-introduce the virus

Question 3

What is an chronic infection

Answer 3

Viruses persist changes within the course of infection

Ongoing ping infection due to new variations

Question 4

What is an antigenic drift

Answer 4

One virus has point mutations due to no proofreading and replicates to give new variant

Question 5

What is antigenic shift in influenza

Answer 5

2 or more viruses exchange RNA fragments and change haemoglutinin on their surface
This generates a new virus

Question 6

What does antigenic shift result in

Answer 6

Pandemics

Question 7

Why do we not have antigenic shift seen in MMR

Answer 7

Genomes are non segmented so you do not get exchange of segments in the virus

Question 8

Does HIV have a cure

Answer 8

No

Question 9

What are the glycoproteins of HIV called

Answer 9

GP120

GP41

Question 10

Which receptors does glycoproteins bind to

Answer 10

CD4 receptor
CXCR4
CCR5

Question 11

Describe the HIV lifecycle initial stages

Answer 11

1) HIV attaches and fuses into the host cell
2) Viral RNA is synthesised to double stranded DNA by reverse transcriptase
3) viral dna is delivered to the nucleus of cell

Question 12

Where does GP120 bind to

Answer 12

CD4 receptors on T cells

Question 13

What are the coreceptors of CD4 T cell surface membrane

Answer 13

CXCR4

CCR5

Question 14

Describe what happens when HIV bins to CD4 receptors on T cell

Answer 14

1) gp120 binds to CD4 receptors
2) this triggers confomational change in gp120
3) This enables GP120 to bind to its coreceptors CCR4 or CCR5
4) this triggers further conformational changes to move GP120 out of the way
5) so GP41 can penetrate into the cell membrane
6) this brings the HIV envelope with close proximity of cells membrane which causes the fusion of the HIV into the cell.

Question 15

What is the stucture of the hiv glycoproteins

Answer 15

GP41 attached to GP120 which is protruding out

Question 16

What happens when the virus has got into the CD4 T cells

Answer 16

Viral RNA undergoes reverse transcription to form double stranded DNA
Double stranded DNA enters nucleus

Question 17

What happens to the double stranded DNA when it enters the nuclues

Answer 17

Integrated into the host genome straight away by enzyme integrate

Question 18

What does the integration of hiv dna into the host genome mean

Answer 18

You cannot get rid of the virus so it is permanent

Question 19

What are the two pathway that can occur when the dsDNA is intergrated into the host genome

Answer 19

Enter latency
Or
Enter productive cycle

Question 20

Describe the productive cycle

Answer 20

Pro-virus DNA is transcribed by MRNA
MRNA is translated To new proteins
Proteins are assembled
New virus is released

Question 21

What are 5 key staged where we can interrupt virus replication and entry

Answer 21

1) binding
2) fusion
2) reverse transcription
4) integration
5) maturation

Question 22

Why type of therapy do use to treat HIV

Answer 22

Multi drug therapy

Question 23

Give an example of a multi drug therapy

Answer 23

2 different NRTIs + 1 NNTRI
Or
2 different NRTIs + 1 protease inhibitor

Question 24

What does NRTI stand for

Answer 24

Nucleoside reverse transcriptase inhibitors

Question 25

Give an example of NRTI

Answer 25

Zidovudine

Question 26

What is the mechanism of action of NRTI

Answer 26

Incorporate into virus dna because it is a nucleoside
Becomes a chain terminator
Inhibits HIV replication

Question 27

What does NNRTIs stand for

Answer 27

Non nucleoside transcriptase inhibitors

Question 28

Give an example of NNTI

Answer 28

Efavironz

Question 29

What is the mechanism of action of NNTI

Answer 29

Binds directly to reverse transcriptase to alter its shape

Nucleotides cannot interact with the enzyme to create DNA

Question 30

Give an example of protease inhibitors

Answer 30

Saquniavir

Question 31

What is the mechanism of action of protease inhibitors

Answer 31

As HIV replicates it produces protease, protease cleaves HIV poly proteins into structural proteins which are assembled to form new virus
Protease inhibitors bind to protease and inhibit cleavage of viral proteins
Prevent HIV from being assembled and released from infected cells.

Question 32

What happens in acute infection

Answer 32

CD4+ T cell decline temporarily
CD8+ T cells increase to get ride of virus
Anti HIV-1 antibodies appear

Question 33

What happens in chronic infection

Answer 33

HIV continues to replicate at low levels for a decade
Gradual decline in CD4+ T cells 
CD8+ remain unaffected 
Antibodies evolve 
Acquisition of macrophage tropism

Question 34

What will HIV turn into when CD4+ T Cells are below 200 cell/ml

Answer 34

AIDS

Question 35

What will be seen in a AIDS blood

Answer 35

CD4+ T cells depletion

HIV specific CD4+/CD8+ EXHAUSTION

Question 36

What are the AIDS defining opportunistic infection

Answer 36

Cryptococcal meningitis 
Toxoplasmosis 
Pneumocystis pneumonia 
Oesophageal candidiasis 
Certain cancers

Question 37

If HIV mutation occur what clinical problem can this lead to

Answer 37

Drug restistance

Question 38

Therefore in which drugs can you get resistance

Answer 38

NNRTI- reverse transcriptase is mutated do NNRTI cannot bind to enzyme
NRTI - mutation in reverse transcriptase mean you get steric hindrance And excision of NRTIs

Question 39

What does excision of NRTIs involve

Answer 39

Pyrophosphorlysis (removes the nucleotides)

Question 40

Why is it difficult to make a HIV vaccine

Answer 40

Genetic variability of HIV
A Glycan shielding covers the envelope glycoproteins
Immune escape: antibody resistance of the new variation of HIV so antibodies cannot neutralise mutated/new HIV