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Chapter 29 Flashcards

HIV-1

1
Q

A retrovirus of HIV-1 was first isolated from

A

blood samples

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2
Q

HIV is considered a descendant of

A

SIV

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3
Q

the origin of HIV is

A

2 SIV -> SIVcpz -> HIV

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4
Q

HIV infects

A

CD4 helper T-cells

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5
Q

Lentivirus is

A

Genus of retroviridae that shows slow progression

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6
Q

Lentiviruses have

A

HIV-1 (1983), HIV-2, SIV, FIV

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7
Q

the progression of HIV-1 infection is typically followed as

A

decrease in CD4-T cells, immuno-compromised, susceptible to opportunistic infections

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8
Q

the three phases of the HIV progression are:

A

acute-infection, clinical latency, AIDS

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9
Q

acute infection comprises

A

entry of virus, localized replication at site of infection, release of virus into the circulation, seeding of lymph nodes throughout body, immune clearance of virus from peripheral circulation, continued replication in lymph nodes

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10
Q

clinical latency comprises

A

replication and destruction of lymph node architecture

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11
Q

AIDS comprises

A

release of virus into the circulation, loss of immune response, susceptibility to opportunistic infection

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12
Q

in AIDS, symptoms are

A

severe dehydration, diarrhea, bacterial infections, susceptible to skin cancer

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13
Q

the lower the virus load setpoint,

A

the slower the progression to AIDS

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14
Q

virus load setpoint is shown during

A

clinical latency after 12 weeks

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15
Q

HIV-1 is pandemic, where transmission is through

A

blood, sex, and breast milk

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16
Q

there are vaccine development with

A

30 candidates

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17
Q

antiviral treatments are done through

A

HAART, combination of at least three different drugs, inhibiting RT and PR

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18
Q

when virion protein R is packaged into the virion, tRNA of HIV is

A

lysine tRNA

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19
Q

general structure of HIV-1

A

conical capsid, VpR with tRNA lysine

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20
Q

genome structure of HIV-1

A

it has six additional ORFs of Vif, Vpr, Vpu, Tat, Rev, Nef

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21
Q

Vpr is structural, because

A

it is a part of the virion that has regulation roles

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22
Q

HIV produces over 25 mRNAs through

A

different splice sites

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23
Q

the 25 mRNAs are grouped in

A

three classes based on size

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24
Q

full length 9 Kb mRNA is used for

A

Gag and Pol (frameshift)

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25
(single splice) 4 Kb mRNA is used for
Env, Vpr (frameshift), Vif, Vpu
26
(double splice) 2 Kb mRNA is used for
Tat, Rev, Nef
27
Vif is
viral infectivity factor
28
Vpu is
virion protein unique to HIV-1
29
Tat is
transactivator of transcripiton
30
Rev is
regulator of expression of virion proteins
31
Nef is
negative effector
32
HIV-1 targets
T cells and macrophages
33
T cells and macrophages have
CD4 receptor on surface
34
additional receptors of
CCR5 for macrophages and CXCR4 for T cells are needed
35
attachment protein is called
gp120 (SU) interacting with both primary and secondary receptors
36
gp41 (TM) is for
mediating fusion with PM
37
the capsid travels to
nucleus and enters via pores
38
the virus needs ds-DNA for
replication
39
Vpr is present in viral particle, carried into newly infected cell for two functions
1) helps virus enter nucleus through pores, required for HIV replication in non-diving cells 2) induces cell cycle arrest in the G2 phase, so viral transcription can be increased with HIV-1 LTR being most active in G2 phase
40
Core goes through RT, and travel through cytoplasm on
microtubule
41
in nucleus, pre-integration complex is composed of
IN, MA, and Vpr with the dsDNA
42
viral latency is regulated by
transcriptional control elements in U3
43
when foreign invader detected, immune response is
activated, along with T-cell activation
44
T-cell activation leads to
activation of cellular TFs: NFkB and NFAT
45
NFkB translocates into
nucleus, and interacts with U3 driving synthesis of the RNA
46
T-cell activation activates
downstream TFs to translocate into nucleus where they bind to U3 to start transcription of proviral DNA
47
NFkB and NFAT recruit
Pol II
48
in the early gene expression, genes encoded in
the 2 kb class are expressed first
49
CRS is
cis-acting repressive sequence of RNA in Gag/Pol and Env ORFs, causing viral mRNAs to be retained in the nucleus
50
with CRS present, the full length 9 kb mRNA is
spliced twice to be transported to cytoplasm for translation
51
the CRS present mRNAs are
retained in the nucleus
52
Tat is
a highly basic protein of early gene that localizes to the nucleus to activate transcription
53
Tat binds to
Tar in nascent viral RNA
54
Tat recruits
Cyclin T and Cyclin-dependent kinase-9
55
CdK9 is to
phosphorylate c-terminus of Pol II, enhancing processivity to increase full-length mRNA
56
TAR is
a RNA element formed in the newly made transcript as a hairpin structure, bound to RNA pol II
57
Rev is
a regulator of expression of virion protein of early gene that mediates nuclear export of LATE mRNAs in the 4 and 9 kb classes
58
Rev binds to
RRE, rev response element in vRNAs, and Exportin1/RanGTP in Env ORF
59
Exportin1/RanGTP is present only in
4 kb and 9 kb, involved in nuclear export pathways
60
RRE located in
Env ORF
61
Rev mRNA can exit from
nucleus to cytosol, to be translated as a protein
62
Rev protein binds to
cellular protein Importin Beta, bringing it to the nuclear pore, and translocated into the nucleus
63
Rev associating with
Exportin1/RanGTP, binding to RRE on mRNA, exits the nucleus
64
Rev and Exportin1/RanGTP dissociates from RRE, and the mRNA is
now translated
65
Nef is
a negative effect protein of early gene for determining pathology
66
With Nef, there is
AIDS-like disease
67
Without Nef, there is
no AIDS-like symptoms. It may be possible to develop an attenuated vaccine
68
Nef's known function is to
decrease surface expression of CD4 and MHC1, enhance virus infectivity, modify multiple parts of cell signalling
69
Nef associates with
the cytoplasmic face of the PM
70
Nef interacts with
the cytoplasmic tail of CD4, recruiting clathrin adpator protein 2
71
Nef with clathrin AP2 undergoes
clathrin-mediated endocytosis of CD4, consequently decreasing CD4
72
Nef interacts with MHC1 by blocking
Golgi to PM trafficing
73
the absence of CD4 and MHC1 results
inhibition of immune response for the infected T-cell
74
Nef associates with some proteins for cytoskeleton to enhance
releasing capsid into cytosol, leading to better infectivity
75
Nef inhibits apoptosis through
associating with Pak2 kinase to increase anti-apoptosis signalling; associating with Ask1 kinase to inhibit apoptosis signalling
76
Vif is
a viral infectivity factor in late gene
77
when Vif is absent, cellular protein Apobe gene gets incorporated into
budding virions from infected cell
78
Once virion infects new cells, Apobe acts as
cytidine deaminase that converts cytosine to uracils in the (-)-strand DNA, resulting in G to A mutation in the (+)-strand during RT
79
in absence of Vif, HIV goes through
hypermutation that inhibits farther viral spread
80
Vif mediates in
degradation of host APOBEC3G through ubiquitination
81
degrading APOBEC3G thorugh ubiquitin ligase protects
the virus from hypermutation
82
mutant APOBEC3G with no deaminase activity retains
some inhibition of HIV
83
A3G also directly inhibits
RT
84
Vpu is
virion protein unique to HIV of late gene
85
Vpu is
transmembrane protein that accumulates in Golgi and Endosomes
86
Vpu has two functions of
degrading CD4 and enhancing virus release from PM
87
Vpu interacts with
CD4 that normally would bind to gp160 in ER lumen, and recruiting beta-TrCP would ubiquitinate the CD4
88
gp 160 is processed alone to be transported to PM, where it serves to
bud out new virions out of the cell
89
Vpu enhances virus release from PM by
helping budding and releasing
90
when mutated, Vpu allows
virions to accumulate on cell surface
91
Vpu counteracts
anti-viral activity of a cellular protein Tetherin
92
Tetherin interacting partially with
cellular PM and viral Env, forming a bridge for a cell to hold a virion for interferon regulation
93
Vpu decreases
tetherin expression, possibly through Vpu-mediated degradation or sequestration
94
immune system is evaded by
viral mutation to consequently alter viral proteins
95
three vaccine types are
killed, attenuated or subunits
96
phase two of vaccine test is on
small population
97
phase three of vaccine test is on
large population
98
first vaccine that went through phase three is
AIDSVAX
99
AIDSVAX targets on
introduction of HIV surface protein gp120 to generate antibodies
100
adenovirus 5 vector with Gag/Pol/Nef is
adeno5 vector used to deliver HIV-1 genes, ineffective
101
recombinant viral vector with synthetic versions of Gag, Pr and Env genes + boosted with gp120
31% reduction in HIV acquisition
102
Canadian HIV vaccine is
killed, no adverse effects, removed Nef and Vpr

BIOL 3155 (16 decks)

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