Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Z MD1 Reproductive Block > HIV pathogenesis > Flashcards

HIV pathogenesis Flashcards

1
Q

what are the 3 most important structural gene groups of HIV

A

env
gag
pol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are the genes encoded by the env genes and what are their functions

A 
gp120 = cell attachment (surface)
gp40 = fusion domain (transmembrane)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the genes encoded by the gag genes and what are their functions

A

structural proteins of the capsid - encase the 2 copies of RNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the 3 important proteins encoded by the pol genes

A

reverse transcriptase
integrase
protease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

explain the 3 steps of HIV fusion with T cells

A
  1. attachment of the gp120 protein to CD4 molecule –> causes structural change in gp120 –> recruits CCR5/CXCR4
  2. binding to CCR5/CXCR4 –> promotes fusion of gp41 peptide
  3. structural rearrangement of gp41 trimer to drive membrane fusion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

when are CCR5 or CXCR4 used

A

CCR5 - early

CXCR4 - late

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

functions of HIV reverse transcriptase

A
  • converts the viral genomic RNA to proviral cDNA

- duplicates the sequences at the end of the viral DNA –> LTRs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

function of HIV integrase

A

catalyses the random integration of HIV cDNA into cell DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what part of the cDNA made by RT acts as the promoter

A

the 5’ LTR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

explain the regulation of the 5’ LTR promotor of the HIV cDNA

A
  • increases expression in response to HIV Tat protein
  • silences HIV expression soon after initial replication
  • responds to cellular proteins made during T cell immune activation to dramatically increase HIV expression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

which HIV enzyme has the greatest error rate and therefore the cause of viral diversity

A

reverse transcriptase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the protein that is made by HIV that is like a protein made by T cells

A

NF-KB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the cis and trans factors that can regulate HIV basal transcription

A
  • cis = chromatin and associated factors (switch off transcription)
  • trans = TFs made by T cells can activate transcription (eg NF-KB)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the 2 major regulatory proteins of HIV

A

Tat

Rev

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

functions of Tat protein

A
  • promotes HIV transcriptional elongation

- inhibits MHC-1 gene transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

functions of Rev protein

A

stabilises and transports unspliced and partially spliced HIV RAN to the cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are the 4 main accessory proteins of HIV

A

Vif
Vpr
Vpu
Nef

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is the overall function of the accessory proteins of HIV

A

prevent MHC-1 presenting HIV peptides to APCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

functions of Vif

A
  • promotes infectivity of cell free virus
  • blocks cell defences targeting ss cDNA
  • degrades APOBEC3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

functions of Vpr

A
  • protein for nuclear import

- cell growth arrest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

functions of Vpu

A
  • promotes MHC-1 and CD4 degradation through direction MHC-1 to proteasome and lysosomal degradation
  • antagonises tetherin
    facilitates the release of fully infectious virions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

functions of Nef

A

down modulates cell MHC-1 and CD4 through lysosomal degradation of MHC-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

how does the HIV virus mature

A
  • ribosome shift causes the icosahedral core of HIV to form a complex rod shape after budding and the GAG polyprotein gets jointed onto Pol
  • the protease activity of the Gag-Pol precursor protein causes cleavage of polyproteins into individual proteins –> assemble into fully infectious virus particles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

in which T cells is HIV latent

A

central (mostly) and transitional memory T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

how is latent HIV reactivated

A

Tat protein activates RAN expression
- causes recruitment of histone acetyl-transferases –> leads to acetylation of histones in chromatin –> opening the DNA promotor for access by RNA polymerase II

26
Q

what are the reasons for HIV persistence

A
  • integrates into the cells that would be in charge of their removal
  • highly mutagenic
  • mechanisms that direct active evasion
  • integration into host DNA
27
Q

what are the 3 phases of untreated HIV

A

primary infection
asymptomatic infection
symptomatic infection and AIDS

28
Q

what is primary infection characterised by

A
  • a rapid and massive loss of the body’s CD4+ T cells
  • initial decline in HIV due to CD4 substrate exhaustion
  • loss of memory T lymphocytes in GALT
29
Q

what is the incubation period of primary HIV infection

A

2-4 weeks

30
Q

in what percentage of people seroconvert if not treated

A

50-95%

31
Q

what are the best tests to test for early HIV infection

A

those that measure viral RNA

32
Q

what is HIV viral load

A

amount of HIV RNA in plasma

33
Q

what are the initial immune responses that contain HIV replication

A
  • high titres of HIV specific Ab

- 5% of total IgG specific for HIV envelope

34
Q

why are Ab against the HIV env protein essentially useless

A
  • does not neutralise it
  • high level of Env glycosylation
  • low immunogenicity of virus bound gp120 oligomers compared to circulating free monomers
  • greatest sequence variability
35
Q

what are the mechanisms by which HIV escapes from the immune system

A
  • sequence variation
  • altered antigen presentation
  • loss of effector cells
  • latency
  • privileged sites of viral replication
36
Q

when is the viral load said to be undectectable

A

when viral load <50copies/ml

37
Q

what predicts survival if you have untreated HIV

A

viral load

38
Q

how does HIV cause indirect destruction of uninfected CD4+ T cells

A
  • cytolysis by HIV specific CT or NK cells
  • incorporation into syncitia
  • immune ACTIVATION of CD4 and CD8 T cells
39
Q

what causes the chronic immune activation leading to T cell depletion in HIV

A

integrity of gut mucosal barrier lost –> microbial products leak into systemic circulation –> immune cells stimulated through TLR –> elevation of pro-inflammatory cytokines –> CD4 T cells enter cell cycle and die, CD8 T cells beome trapped in lymph nodes, B cells make auto-Ab

40
Q

what are the results of depleted T cells on the rest of the immune system

A
  • reduced T cell help for B cells and macrophages
  • reduced killing of bacteria by neutrophils
  • increased autoantibodies by B cells, and reduced killing of encapsulated bacteria
  • reduced phagocytosis, chemotaxis and killing by macrophages
  • reduced NK function
41
Q

at what CD 4 Tcell level do you start to get opportunistic infections

A

less than 200cells/ml

42
Q

mean survival after untreated AIDS

A

1.3 years

43
Q

what factors determine disease progression

A
  • strain of HIV virus
  • coinfection with hepatitis G
  • HLA type
  • immunology
  • age
44
Q

what are the main general types of antiviral therapy for HIV

A
  • RT inhibitors
  • fusion/entry inhibitors
  • protease inhibitors
  • integrase inhibitors
45
Q

what is the reason for combinational anti-HIV therapy

A

improbability of multiple different viral changes to combat all 3 drugs

46
Q

how do the fusion/entry inhibitors anti-HIV drugs act

A

binds to CCR5 or CXCR4 on human cells to block it interacting with envelope proteins on HIV

47
Q

difference between nucleoside and nucleotides

A 
nucleoside = no phosphate groups
nucleotide = phosphate group
48
Q

how does acyclovir work

A

it is a nucleoside analogue that lacks the 3’ hydroxyl group required to form DNA polymer

49
Q

how is acyclovir encorporated into the cell

A

herpes virus thymidine kinase has to perform the first phosphorylation of the acyclovir. Cellular kinases do the further 2 phosphorylations

50
Q

what is the difference between acyclovir and valacyclovir

A

valacyclovir has an additional valine side chain that increases the passage of the drug through the digestive tract and into the circulation (improved oral bioavailability)

51
Q

what is ribavirin

A

a guanosine analogue that inhibits replication of many DNA and RNA viruses in vitro

52
Q

what are the uses for ribavirin

A
  • RSV bronchiolitis and pneumonia
  • influenza
  • haemorrhagic fevers
  • hep c
53
Q

what are the nucleoside reverse transcriptase inhibitors for HIV-1

A

thymidine, cytidine and guanosine analogues that are used by viral RT in preference to cellular nucleosides causing transcription termination

54
Q

what is zidovidine

A

thymidine analogue

55
Q

how do non-nucleoside reverse transcriptase inhibitors for HIV-1

A

directly inhibit the RT enzyme by other mechanisms

56
Q

what is raltegravir

A

integrase inhibitor

57
Q

how do integrase inhibitors work

A

blocks strand transfer of viral DNA into host DNA

58
Q

how do protease inhibitors of HIV work

A

they bind tightly to the enzyme active site preventing their action

59
Q

what are two drugs that are protease inhibitors

A

indinavir

nelfinavir

60
Q

what were the long term complications of HAART in the 1st decade

A

lipoatrophy
lipodystrophy
neuropathy
multi-drug resistance

61
Q

why does HAART fail to cure HIV

A

a small proportion of HIV remains latent in:

  • resting memory T cells
  • reservoirs (brain, gut, testis)
62
Q

even though patients are not dying of OI anymore with HIV, what are the long term consequences now

A 
ongoing immune activation, which leads to:
- decreased endothelial activation
- increased monocyte activation
- dyslipidaemia
- hypercoagulation
- endothelial dysfunction
leading to "diseases of old age"

Z MD1 Reproductive Block (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions