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Immunology 3 > #7 Retro II > Flashcards

#7 Retro II Flashcards

1
Q

For complex retro virus we see 6 accessory proteins of HIV

A

Vif, Vpr, Vpu, Nef, Tat, Rev

***key for pathogenesisi

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2
Q

Regulatory Proteins =

crucial for viral replication and are good targets for therapy

A

Tat and Rev

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3
Q

Accessory protein thats the transactivator of transcription—absolutely necessary for transcription

A

Tat:

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4
Q

Regulator of Virion expression—allows structural gene expression by promoting transport of unspliced RNA from nucleus to cytoplasm

A

Rev

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5
Q

Rev does:

A

Regulator of Virion expression—allows gene expression by promoting transport of unspliced RNA from nucleus to cytoplasm
“rev like reverend… promotes the ‘unholy (unspliced) RNA out of nucleus.. GET THEE OUT of the hold nucleus! !!

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6
Q

Tat does:

A

Accessory protein thats the transactivator of transcription—absolutely necessary for transcription
“i’ll buy tat and tat and tat (think transactions!)

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7
Q

Restriction Factor—viral proteins that overcome cell defenses or ‘restrictions’

A

Vif

Vpu

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8
Q

: promotes virion release from cells.. .inhibits host protein ‘tetherin’ that inhbits viral release from cell

A

Vpu

“viron promotor usher” because he ushers people out

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9
Q

causes cellular antiviral protein (deoxycytidine deanimase) to be degraded

A

Vif: Virion Infectivity Factor

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10
Q

inhibits host protein ‘tetherin’ that inhbits viral relesase from cell

A

Vpu

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11
Q

Why does Vif destory deoxycytidine deanimase

A

otherwise it’s encorporated into new virions where bock RT in next cell by inducing massive mutations in viral dsDNA

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12
Q

Vif does:

A

destroys deoxycytidine deanimase bc when if its incorporated into new virions it blocks the RT~~ get bunch of mutations

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13
Q

IG retroviruses have 1 receptor for HIV ______which is the initial receptor present on immune cells

A

—CD4

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14
Q

main population depleated in AIDS

A

CD4T helpers

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15
Q

Role of DC cells in HIV
can they bind?
are they infected?

A

DC can bind HIV but aren’t productivey infected; instead assist with viral dissemination (bring virus back to lymph node where there’s high populatuion of CD4 cells)

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16
Q

These can be ________infected but not efficiently killed and serve as a reservior of virus produciotn

A

Macrophages

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17
Q

***for HIV, CD4 binding is required but NOT sufficient to cause membrane fusion bc

A

NEED a co-R

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18
Q

Infection of _______ in the brain infection~contribution to AIDS dementia

A

Microglia

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19
Q

see these infect primarily T cells and macrophages but NOT T-cell lines

A

M-tropic

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20
Q

a. responsible for initial infection, transmission, and predominates in Asymptomatic ind

A

M-tropic

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21
Q

M-tropic infect

A

T cells and macros but NOT Tcell lines

cause initial infection/transmission/seen in asympotomatic ind

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22
Q

infects primary T cells and T-cell lines, NOT macrophages

A

T-Tropic

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23
Q

associated with disease progression, arise in AIDS stage of infection

A

T-Tropic

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24
Q

T-tropic infects which cells

predominates when

A

primary T cells AND tcell lines but NOT macrohpages

disesease progression… seen during AIDS

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25
Q

co-recpeotor for M-tropic HIV

A

CCR5

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26
Q

CCR5 receptor for chemokines: (name 3) can specifically inhibit M-tropic HIV by occupying the receptor

A

RANTES, MIP-1α, MIPβ—these chemokines

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27
Q

RANTES, MIP-1a, MIPB chemokines work to slow progression of HIV by

A

inhibiting M-tropic binding to CCR5 co receptor (they bind it themselves

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28
Q

co-receptor for T-Tropic

A

CXCR4:

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29
Q

natural ligand is cytokine stromal derived factor 1 (SDF-1) that can

A

block T-tropic HIV infection

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30
Q

What can block T-Tropic infection by competinv for CXCR4

A

cytokine stromal dereived factor

SDF-1

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31
Q

Basis for strain tropisms

A

a. Envelope sequence of di HIV types have preference for dif co-receptors
b. Most concern is for M-tropic virus bt it is source of person-person transmission

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32
Q

Most concern is for ______ virus bt it is source of person-person transmission

A

M-tropic

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33
Q

rare ind remain seronegative despite high-risk behavior and presumed viral exposure dt

A

b. 32bp-depletion of CCR5 gene ∆32

–see non-funx CCR5 (~10% of caucasions heterozygous and 1%homo)

34
Q

c. WT: WT

A

—get infected and progress to disease normally

35
Q

d. WT:∆32:

A

get infected and progress to disease more slowly (express ½ as much normal)

36
Q

e. ∆32:∆32—

A

highly resistant to infection.. people are normal but don’t have CCR5 expressed on cells

37
Q

Fusion Process—

  1. Env initially contacts_____ and induce a conformation change in Evn
  2. Change will cause exposure of the____
  3. _____ ‘fusion domains’ are exposed and fuse
A

CD4
co-receptor binding site
gp41

38
Q

______ peptides form and instert into cell

A

Fusion

39
Q

Co-R engagement triggers a _______ of the N and C terminal helical regions of gp41 which brings membrane together and fuses them

A

‘snapback’

40
Q

Fusion process overview

A
  1. Env initially contacts CD4 and induce a conformation change in Evn
  2. Change will exposure the co-receptor binding site
  3. gp41 ‘fusion domains’ are exposed and fuse
  4. Fusion peptides form and inster into cell
  5. Co-R engagement triggers a ‘snapback’ of the N and C terminal helical regions of gp41 which brings membrane together and fuses them
41
Q

How does snapback happen and what is it’s purpose

A

Co-R engagement triggers a ‘snapback’ of the N and C terminal helical regions of gp41 which brings membrane together and fuses them
**like chinese finger trap!!

42
Q

Can we block this Snapback mechanism?

A

YES! T20 (Fuzeon) can bind the N-term helical region to block snap-back

43
Q

T20 (Fuzeon) can

A

bind the N-term helical region to block snap-back

44
Q

HIV is IG at the mucosal surface or by blood products and is spread to lymph node via

A

DC cells biding and carrying HIV there

45
Q

Once virus infects T cells in lymph nodes (thanks a lot DC cells.. ya fuckers) and spills into circulation causing

A

viremia

46
Q

During asymptomatic phase, FCD traps virus, keeps viremia ____ but nodes (especially _____) are major site of replications

A

low

GALT

47
Q

deteriorates in late infection

A

~~ GALT

48
Q

What traps our virus in asymptomatic phase to viremia low

A

FCD

49
Q

Direct killing of CD4 T by HIV is due to

massive reproduction =

A

mmb leakage and death

50
Q

Whats the bystander effect to kill cells during HIV

c. Apoptosis induced by infection—some evidence that cells undergo apoptosis even if infection is unproductive

A

Syncytia (fuse cells) induced by fusion of infected cell w/ unifected cells
-via Env or infected cell interacts with CD4/CCR5 on unifected cell); cells usually die and could kill uninfected cells

51
Q

_____ (fuse cells) induced by fusion of infected cell w/ unifected cells
-via Env or infected cell interacts with ______ on unifected cell); cells usually die and could kill uninfected cells

A

Syncytia

CD4/CCR5

52
Q

Indirect effects on infected CD4 cells

–immune response

A

kills infected cells, important for clearing initial viremia

53
Q

INdirect effects on infected CD4 cells

________ may bind uninfected cells, now susceptible to ADCC

A

soluble gp120

54
Q

Impairment of immune system fnx

CD4 T cell fnx altered, loss of CD4 and T cell help, leads to

A

severly compromised immune system

55
Q

What happens to infected macrophages with HIV and ability to work effectively

A

b. Infected macrophages dysfunctional→ aberrant immune fnx

56
Q

Acute infection and seroconversion

-initially we see burst of virus production coinciding with:

A

a. Initial burst of virus production coincides w/ decreased CD4T cells

57
Q

Acute infection:
Early vigorous CTL, subsequent humoral response with FCD help, clears viremia… immune response only ‘appears’ to control infection because

A

; high level of virus production persists in lymph/GALT

58
Q

Asymptomatic phase:

contineud strong immune response, gradual decline in ______

A

CD4 counts

progression measured by CD4 counts and CD4:CD8 ratio

59
Q

‘vial load’ by measuring _____ by PCR and pts with lower set point have better prognosis

A

RNA

60
Q

a lower viral set point of RNA means patient has:

A

better outcome

61
Q

Symptomatic/AID phase: late in infection
CD4 cells depleted below _____and immune system begins to fail
~~viremia increases, pts suseptible to many opportunisti infections

A

200

62
Q

Point of tests to detect HIV

A

indentify infected person to start tx
identify carriers
follow course of ts

63
Q

Serology cannot detct newly infected until

A

4-6 weeks post infection

64
Q

Seriology inclucdes
Ab Elisa:
Ag Elisa
Western blot

A

Ab Elisa~ initial screeing, detect Ab to virus
Ag ELISA: detects p24 capside antigen earlier then Ab
Western blot: confimation test

65
Q

Ag ELISA: detects _______earlier then Ab

A

p24 capside antigen

66
Q

detects virus in blood

A

RNA RT-PCR

67
Q

Use of reat time PCR

A

quantitateve virus in blood
VERY sensitive and detects virus before seroconversion (for high risk/newborns)
gauges viral load in asymptomatics at low titers

68
Q

quantitateve virus in blood
VERY sensitive and detects virus before seroconversion (for high risk/newborns)
gauges viral load in asymptomatics at low titers

A

RT-PCR

69
Q

RT inhibitor: nucleoside/nonnucleoside analogs:

A

(AZT ect >16 drugs)
a. effective but drug resistant strains appear rapidly (billion virus replication per/day so they are prone to RT errors at 5errors/genome)

70
Q

Protease inhibotors (>11 drugs):

A

exteremly effective, reduce viral load by 30-100 x alone, but still see resist.

71
Q

Fusion inhibitors (T-20) aviable but

A

$$$$ and must be injected

72
Q

Entry inhibitors:

A

Maraviroc—CCR5 co-R antagonist

73
Q

Raltegravir

A

Integrase inhibitor

74
Q

HAART is

A

Highly Active Anti-Retroviral Therapy

Considereable success of cocktails of triple therapy

75
Q

a. viritually eliminates virus production in some ind for years w/ undetectable viral load, increase CD4 count and lots of clinical benefit
~~ long term its toxic

A

HAART

76
Q

HAART helped us discover replication dynamics of HIV and HIV ½ life
estimate time to clear free virus and infected T cells=
other ‘compartments’ w/ longer ½ lives like Macrophage or FDC =

A

2 months (infected T cells)

1-2 years (macrophage of FCD)

77
Q

Infected memory T cell: long lived, can detect virus from those on HAART for more then

A

5 years and would need 75 years to clear them!

78
Q

Issues with HAART

A

a. not all pts respond to HAART
drug regimen is hard to follow (but getting easiert w/ once a day pills)
toxic effects seen in long term HAART users
‘inaccessbible’ pool of virus

79
Q

Effort to devo drugs with less toxicity in the pipeline

A

New attacment inhibitors or anti-CD4 antibody
New CXCR4 and ‘dual receptor’ inhibitors and anti-CCR5 antibody
RT inhibitors to common drug resistant viruses
New integrase inhibitors
Maturation inhibitors that work on gag and gag-pol proteins

80
Q

Vaccine for HIV

A

Saw a ‘prime boost’ approach… in thialand~ 30% less liekly to HIV/AIDS (51 if the 8,000) people given the vaccine and 74 of them received dummy shots
–responders had a novel, broadly neutralizing antibody; hope is finely tuned vaccine can elicit it

Immunology 3 (20 decks)

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