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
Q

in keratinocytes, the late promoters direct transcription of RNAs that code for

A

E1 and 2 that polyadenylated early, L1 and 2 that polyadenlyated late

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26
Q

L1 and 2 are for

A

majro and minor capsids, respectively

27
Q

hte increased level of these late proteins contributes to

A

the shift to vegetative DNA replication, during which many thousands of viral DNA molecules per cell are made.

28
Q

viral E1 and E2 proteins bind to

A

the replication origin and direct initiation of DNA replication

29
Q

regulatory DNA sequences known as the long control region (LCR) contains

A

the viral origin of DNA replication as well as enhancer sequence that control viral gene expression

30
Q

the viral E1 protein is a DNA helicase that binds to

A

the origin of replication and locally unwinds the viral DNA

31
Q

the viral E2 binds to

A

distinct sites near the replicaiton origin, and forms a complex with the E1 protein

32
Q

E2 also binds to

A

mitotic chromosomes and is believed to aid in the correct segregation of the viral genomes between the two daughter cells

33
Q

E1’s function is

A

DNA helicase, binds to replication origin, initiates DNA replication

34
Q

E2’s function is

A

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
Q

E4’s function is

A

unknown; most abundantly expressed viral protein, binds keratins and may help virus maturation and release

36
Q

E5’s function is

A

small, membrane-associated protein, enhances growth factor responses in infected cell, stimulates cell proliferation

37
Q

E6’s function is

A

directs ubiquitin-mediated degradation of cellular p53 and other target proteins, inhibits cell-cycle block and apoptosis

38
Q

E7’s function is

A

binds to and degrades Rb protein, releases E2F, activates cell cycling and DNA replication genes, stimulates cell and viral DNA replication

39
Q

L1’s function is

A

major capsid protein

40
Q

L2’s function is

A

minor capsid protein, helps encapsidate viral DNA

41
Q

a gene that contributes to the induction of cancer

A

HPV E7, Ad E1A, SV40 LTAg, Ad E1B 55K, HPV E6

42
Q

a gene that contributes to the repression of cancer

A

pRB (retinomablast (Rb)) and p53 (mutated in 50% of human tumors)

43
Q

pRB interacts with

A

HPV E7, Ad E1A and SV40 LTAg

44
Q

p53 interacts with

A

SV40 LTAg, Ad E1B 55k and HPV E6

45
Q

E7 is important in

A

inducing cellular DNA synthesis

46
Q

E7’s most significant target is

A

the retinoblastoma

47
Q

the Rb protein is a major regulator of the cell cycle, and functions through

A

its ability to bind to and repress the activity of the E2F

48
Q

the normal interaction of Rb and E2F

A

blocks transcription of cell-cycles genes

49
Q

When E2F is freed from bound Rb,

A

it can induce the expression of a number of genes to initiate cDNA synthesis, from the G1 to S

50
Q

E7 from oncogenic types bind to

A

Rb more strongly than non-oncogenic types

51
Q

CDK-cylcin complex can free Rb from E2F through

A

phosphorylation of Rb, activating E2F free

52
Q

unscheduled cDNA synthesis induces

A

apoptosis, and this process is dependent on the activity of the cellular p53 protein

53
Q

p53 is activated and stabilized by

A

E7 and DNA damage

54
Q

p53 induces

A

apoptosis

55
Q

p53 activates transcription of

A

p21/Bax

56
Q

p21 activates

A

cell cycle arrest

57
Q

Bax induces

A

apoptosis

58
Q

p53 can be ubiquitinated by

A

E6AP

59
Q

E6AP binds to p53 when

A

E6 binds to E6AP

60
Q

p53 is not mutated in

A

cervical cancers caused by HPV

61
Q

E6 and E7 become integrated into a

A

cellular genome

62
Q

expression of E6 and E7 results in

A

transformation into a cancer cell

63
Q

no virus replication in

A

transformed cells

64
Q

HPV vaccines VLPs are

A

“cancer” vaccine and have Gardasil and Cervarix