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Chapter 22 Flashcards

Papillomavirus

1
Q

The basic structure of papillomavirus

A

non-enveloped icosahedral with T=7 capsid, circular ds-DNA in minichromosome (cellular histones)

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2
Q

the gene is replicated by

A

cDdDp

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3
Q

the gene is transcribed by

A

cDdRp

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4
Q

HPV type 1

A

soles of feet, deep plantar warts

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5
Q

HPV type 2, 4, 7

A

hands, common warts

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6
Q

HPV type 6, 11

A

condyloma

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7
Q

HPV type 16, 18, 31

A

genital tracts, cervical cancer

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8
Q

HPV binds to

A

Heparin and integrin

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9
Q

HPV infection at

A

non-differentiated basal stem cells of the epithelum

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10
Q

HPV virions are taken up by

A

endocytosis

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11
Q

viral DNA enters the nucleus, maintained as

A

a free, circular minichromosome

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12
Q

early genes are transcribed, permitting an initial replication phase that results in

A

50 to 100 copies of DNA per cell

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13
Q

genomes replicate on average about once per cell cycle as

A

the basal cells divide and the viral genomes are distributed equally among the daughter cells (plasmid replication)

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14
Q

when the basal cells become committed to the pathway toward terminally differentiated epithelial cells (keratinocytes),

A

there is a burst of viral DNA synthesis, known as vegetative replication

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15
Q

during the vegetative replication, late genes

A

L1 and L2 are expressed, producing the viral capsid proteins

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16
Q

progeny virus particles are assembled in

A

the nucleus, and are released upon cell death and shedding at the surface of lesions.

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17
Q

genome structures of what types are focused here?

A

type 16 and 31 that cause cervical cancer

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18
Q

virions are constructed from

A

72 capsomeres, each containing 5 molecules of the major capsid protein L1 as well as one molecule of the minor capsid protein L2

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19
Q

how many ORF expressed in the HPV lifecycle?

A

8 genes with 6 early replicate genes and 2 late structural capsid genes

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20
Q

all papillomavirus mRNAs are transcribed from

A

only one of the DNA strands

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21
Q

how many promoters are there in the HPV genome?

A

an early promoter located upstream of the E6 gene; a late promoter located upstream of the E1 upstream

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22
Q

in undifferentiated basal epithelial cells, the early promoters direct transcription of RNAs that code for

A

E6, 7, 1, 2, 5 then, the early primary transcript is polyadenylated AAUAAA at a site downstream of the E5 gene

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23
Q

E5, 6 and 7 are for

A

cell proliferation

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24
Q

E1 and 2 are for

A

plasmid replication (BEC) and vegetative replication (keratinocytes)

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25
in keratinocytes, the late promoters direct transcription of RNAs that code for
E1 and 2 that polyadenylated early, L1 and 2 that polyadenlyated late
26
L1 and 2 are for
majro and minor capsids, respectively
27
hte increased level of these late proteins contributes to
the shift to vegetative DNA replication, during which many thousands of viral DNA molecules per cell are made.
28
viral E1 and E2 proteins bind to
the replication origin and direct initiation of DNA replication
29
regulatory DNA sequences known as the long control region (LCR) contains
the viral origin of DNA replication as well as enhancer sequence that control viral gene expression
30
the viral E1 protein is a DNA helicase that binds to
the origin of replication and locally unwinds the viral DNA
31
the viral E2 binds to
distinct sites near the replicaiton origin, and forms a complex with the E1 protein
32
E2 also binds to
mitotic chromosomes and is believed to aid in the correct segregation of the viral genomes between the two daughter cells
33
E1's function is
DNA helicase, binds to replication origin, initiates DNA replication
34
E2's function is
binds to specific sites on viral DNA, enhances binding of E1 to replication origin, activates or represses transcription of viral genes, binds to mitotic chromosomes and aids in segregation of viral genomes between two daughters cells
35
E4's function is
unknown; most abundantly expressed viral protein, binds keratins and may help virus maturation and release
36
E5's function is
small, membrane-associated protein, enhances growth factor responses in infected cell, stimulates cell proliferation
37
E6's function is
directs ubiquitin-mediated degradation of cellular p53 and other target proteins, inhibits cell-cycle block and apoptosis
38
E7's function is
binds to and degrades Rb protein, releases E2F, activates cell cycling and DNA replication genes, stimulates cell and viral DNA replication
39
L1's function is
major capsid protein
40
L2's function is
minor capsid protein, helps encapsidate viral DNA
41
a gene that contributes to the induction of cancer
HPV E7, Ad E1A, SV40 LTAg, Ad E1B 55K, HPV E6
42
a gene that contributes to the repression of cancer
pRB (retinomablast (Rb)) and p53 (mutated in 50% of human tumors)
43
pRB interacts with
HPV E7, Ad E1A and SV40 LTAg
44
p53 interacts with
SV40 LTAg, Ad E1B 55k and HPV E6
45
E7 is important in
inducing cellular DNA synthesis
46
E7's most significant target is
the retinoblastoma
47
the Rb protein is a major regulator of the cell cycle, and functions through
its ability to bind to and repress the activity of the E2F
48
the normal interaction of Rb and E2F
blocks transcription of cell-cycles genes
49
When E2F is freed from bound Rb,
it can induce the expression of a number of genes to initiate cDNA synthesis, from the G1 to S
50
E7 from oncogenic types bind to
Rb more strongly than non-oncogenic types
51
CDK-cylcin complex can free Rb from E2F through
phosphorylation of Rb, activating E2F free
52
unscheduled cDNA synthesis induces
apoptosis, and this process is dependent on the activity of the cellular p53 protein
53
p53 is activated and stabilized by
E7 and DNA damage
54
p53 induces
apoptosis
55
p53 activates transcription of
p21/Bax
56
p21 activates
cell cycle arrest
57
Bax induces
apoptosis
58
p53 can be ubiquitinated by
E6AP
59
E6AP binds to p53 when
E6 binds to E6AP
60
p53 is not mutated in
cervical cancers caused by HPV
61
E6 and E7 become integrated into a
cellular genome
62
expression of E6 and E7 results in
transformation into a cancer cell
63
no virus replication in
transformed cells
64
HPV vaccines VLPs are
"cancer" vaccine and have Gardasil and Cervarix

BIOL 3155 (16 decks)

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