Chapter 13 Part 2 Flashcards Preview

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Flashcards in Chapter 13 Part 2 Deck (80):
1

What cells are specialised for type I interferon production early in viral infection?

plasmacytoid DCs

2

What is the benefit of a segmented genome?

the ability ot reassort during viral replication

3

What is the fucntion of hemagglutinin on influenza?

repsonseibl for viral binding to and entry into cells

4

What is antigenic drift?

emergence of point mutations to alter binding sites-- can grow in cell immune to previous strain but as T cells and some antibodies can recognise epitopes that have not been altered will only get a mild disease

5

Waht is antigenic shift?

reassortment of the segmented RNA genomes of 2 different influenza viruses when they are able to infect the same cell reuslting in large changes in their haemagglutinin so T cells and antibodies to previous infections are not protective

6

What is a neutralising antibody?

prevent the virus from binding and infecting cells

7

What is dislocation?

when viruses catalyse the degradation of newly synthesised MHC-I molecules by initiating hte pathway normall used to degrade misfoleded ER proteins by directing them back into the cytosol and the ERAD pathway for disposal

8

How does CMV evade NK cytolysis?

produces a homolog of HLA class I - UL18 which binds LIR-1 on nk cells providing an inhibitory signal

9

What is the function of cytosolic ICP47 produced by herpes simplex?

prevents peptides from binding to TAP in the cytosol

10

What is hte function of US6 protein produced by CMV?

interferes with the ATP-dependent transfer of peptides through TAP

11

What is the function of E19 produced by adenovirus?

competes with tapasin and inhibits peptide loading onto nascent MHC-I molecules

12

What is the function of mK3 protein produced by murine herpes simplex virus?

directs the addition of ubiquitin subunits with K48 linkages resulting in degradation via proteasome

13

What cytokine homolog does CMV use to impair antiviral responses?

cmvIL-10 which downregulates pro-inflammatory cytokines

14

What do herpes viruses express in order to undergo a lysogenic phase?

express the latency associated transcript

15

What is the function of the latency associated transcript?

suppresses the transcription of the remaining viral genome and produces factors that interfere with host cell apoptosis

16

How does EBV enter B cells?

using CD21 (CR2) and MHC-II

17

What is the function of EBNA1 produced by EBV?

interacts with teh proteasome to prevents its own degradation into peptides that would otherwise elicit a T cell repsonse

18

What are the differences between HIV-1 and HIV-2?

HIV-2 is only really found in West Africa; HIV-1 replicates to higher viral loads in the blood and is more easily transmitted, HIV-2 is rarley vertically transmitted

19

what is the most common variant of HIV-1?

group M

20

What makes up the HIV viral spike?

gp120/gp41

21

What is the function of the RNA transcripts produced from the integrated viral DNA?

mRNAs to direct synthesis of viral proteins and the RNA genomes of new viral particles

22

What group of viruses does HIV belong to?

lentiviruses

23

What are the 3 cell targets of HIV?

CD4 T cells; macrophages and DCs

24

What is cellular tropism?

its ability to enter particular cell types

25

What determines HIV's cellular tropism?

expression of specific receptors fro the virus on the surface of those cells

26

What are the major coreceptors for gp120 fusion and entry?

CCR5 and CXCR4

27

Which cells predominantly express CCR5?

subsets of effector memory CD4 T cells; DCs and macropahges

28

Which cells predominantly express CXCR4?

naive and central memory CD4 T cells

29

What happens when gp120 binds CD4?

undergoes a conformational change that exposes a high-affinity site that is bound by the coreceptor

30

What does binding of the coreceptor to gp120 cause?

gp41 unfolds and inserts a portion of its structure (fusion peptide) inot the plasma membrane of hte target cell

31

What is found in the viral nucleocaspid?

viral genome and associated viral proteins

32

How many genes does HIV have?

9

33

What is the form of DNA produced by reverse transcriptase?

cDNA

34

What is used by integrase to integrate the cDNA into host DNA?

LTRs that reside at each end of the viral genome

35

What is the integrated cDNA copy known as?

provirus

36

What is the function of the gag gene?

encodes structural proteins of the viral nucleocapsid core

37

What is the function of pol?

encodes enzymes involved in viral replication

38

What is the function of env gene?

encodes viral envelope glycoprotein

39

What 3 enzymes does pol encode?

reverse transcriptase; integrase; viral protease

40

How are gag and pol translated?

as long polypeptide chains that are then cleaved by pol

41

What is the product of the env gene?

gp160

42

What is gp160 cleaved into?

gp120 and gp41

43

What initiates transcription of hte provirus following integration?

host transcription factors which are induced during activation

44

What is the function of Tat?

enhances transcription from hte provirus and binds to the RNA transcripts, stabilising them in a form that can be translated

45

What is the function of Rev?

binds to singly spliced or unspliced transcripts and transports them to the cytosol

46

What si the long-lived latency of HIV related to?

it is a consequence of the toprism of the virus for CD4 T cells

47

What is the function of vif?

affects particle infectivity

48

What is the function of viral protein R?

transport of DNA to nucleus, augments virion production, cell cycle arrest

49

What is the function of viral protein U?

promotes intracellular degradation of CD4 and enhances release of virus from cell membrane

50

What is the function of nef?

augments viral replication in vivo and in vitro. decreases Cd4, MHC-I and II expression

51

What 2 transcription factors can initiate transcription of the viral genome?

NFkB and NFAT

52

How may activation of NFkB take place independetly of antigen?

activation of effector-memory T cells can occur by cytokines

53

How does Tat work?

binds to a transcriptional activation region in the LTR which recruits cellular cyclin T1 and its partner, CDK9 to form a complex which phosphoryaltes RNA polymerase and enchanes its ability to generate full-length transcripts of the vrial genome

54

How does Rev work?

binds to Rev response element- a specific viral RNA sequences to prevent degradation of incompletely spliced mRNA transcripts by the host

55

How does Nef augment viral replication?

lowers the threshold for TCR signalling and downregulates CTLA-4 which results in greater and more sustained T cell activation that promotes viral replication

56

How does Vif work?

acts to overcome a cytidine deaminase called APOBEC which catalyzes the conversion od deoxycytidine to deoxyuridine in reverse transcribed viral cDNA thereby destroying its ability to encode protein

57

How does Vpu work?

required to overcome tetherin which inserts into both the plasma membrane of the host cell and the envelope of hte mature virion to block its release

58

How does Vpr work?

target restriction factor SAMHD1, which limits the intracellular pool of deoxynucleotides available for viral cDNA synthesis

59

In what forms can the virus be transmitted?

free infectious particles or via infected cells for which the virus has tropism

60

Why does inital viral replication favoured in Th1 and Th17 cells?

they express CCR5- naive T cells and Th2 don't

61

What strains of virus are typically required for transmission and why?

CCR5-tropic R5 strains as CCR5 dominates on CD4-expressing immune cells resident at the major sites of viral transmission;epithelial cells of the rectum and endocervix express CCR5 so R5 can translocate

62

How can HIV bind to DCs?

binding of viral gp120 to CTLRs eg langerin; mannse receptor and DC SIGN-- allows HIV to travel to lymph nodes

63

Where do the highest number of CD4 T cells in the body reside?

GALT

64

How may the depletion of immune cells in the gut coumpound rapid production of virus in the GALT?

result in barrier breakdown and translocation of constituents of the microbiota which increases immune cell activation

65

What is the viral set point?

level of virus that persists in the blood plasma after development of CTL response and antibody production which occurs during the acute phase to control high viraemia

66

What is the viral set point indicative of?

future disease progression

67

What does the strong selectie pressure of hte antiviral immune response result in?

selection for HIV escape mutants that are no longer detected by the adaptive immune cells- many viral variants

68

What happens to the dominanat viral type?

in about 50% it swithces from R5 to X4 variants which results in progression to AIDs

69

What are the overall functions of the R5 and X4 variants?

R5 variants are critical for HIV transmission whereas X4 variants that emerge under selective pressure contribute to disease progression

70

What is the correlation between the strength of CD4 T cell proliferative responses to HIV antigen and viral load?

inverse

71

What are the 2 important aspects of hte antibody resposne to HIV?

generating neutralising antibody against gp120 and gp41 in order to block viral attachment or entry; generating nonneutralising antibodies that target infected cells for ADCC

72

What are broadly neutralising antibodies?

antibodies able to block infection by multiple viral strains

73

Why is homozygosity of HLA class I alleles associated with more rapid disease progression?

T cell response to infection is less diverse

74

Give examples of HLA class I alleles associated with greater prognosis?

HLA-B57; HLA-b27; HLA-B13- delay HIV-1 escape

75

Why do ARTs not prevent the release of virus?

cells that are already infected as provirus is already established so reverse transcriptase and integrase aren't needed and inhibition of protease does not stop virus being released

76

What causes the increase in cD4 T cells with HAART?

redistribution of CD4 T memory cells from lymphoid tissues into circulation as viral replication is controlled; reduction in immune activation so reduces killing of infected CD4 T cells by CD8 cells; emergence of naive T cells from the thymuc

77

What is the function of APOBEC?>

causes extensive mutation of newly formed HIV cDNA to destroy its coding and replicative capacity

78

What are quasi-species?

variants of HIV that develop from a single foudner virus

79

Which viruses share the formation of quasi-species?

all lentiviruses

80

which HIV gene is respondible for inhibiting the restriction factor SAMHD1?

Vpr