Epstein-Barr Virus Flashcards

1
Q

What percentage of human cancers are estimated to be associated with viruses?

A

15-20%

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2
Q

How can viruses contribute to cell transformation?

A

Carrying transforming genes within their own genome.

Causing host DNA damage during their life cycle and affecting host transforming genes.

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3
Q

What are the three subfamilies of human herpes viruses?

A
  1. Alphaperpesviruses (HSV-1, HSV-2, VZV)
  2. Betaherpesviruses (CMV, HHV-6, HHV-7)
  3. Gammaherpesviruses (EBV, HHV)
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4
Q

When are reactivations of human herpes viruses most likely to occur?

A

When carrier is immunosuppressed.

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5
Q

Name 3 diseases associated with EBV primary infection.

A
  1. Infectious mononucleosis (glandular fever)
  2. Chronic active EBV infection
  3. X-linked lymphoproliferative disease
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6
Q

What are the symptoms of glandular fever?

A

Fever, lymphadenopathy and pharyngitis.

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7
Q

What are the symptoms of chronic active EBV infection?

A

Sever illness of more than 6 months, histologic evidence of organ disease, and demonstration of EBV antigens or EBV DNA in tissue (mimics fatigue syndrome).

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8
Q

What are the symptoms of X-linked lymphoproliferative disease?

A

Inherited disease of males, absence of functional SAP gene impairs the normal interaction of T and B cells resulting in unregulated growth of EBV-infected B cells.

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9
Q

Give 3 EBV associated diseases related to reduced immunity.

A
  1. PTLD (post transplant lymphoproliferative disease) - a tumour often found in organ transplant patients.
  2. Oral hairy cell leukaemia - nonmalignant hyperplastic lesion of epithelial cells, usually in AIDS patients, but also in other immunosupressed patients.
  3. Chronic interstitial pneumonitis - in AIDS patients.
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10
Q

Name 6 cancers which are associated with EBV infection.

A
  1. Nasopharyngeal carincoma
  2. Burkitt’s lymphoma
  3. Hodgkin’s disease
  4. Lymphoproliferative disease and lymphoma
  5. Gastric carcinoma
  6. Nasal NK/T-cell lymphoma
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11
Q

Describe the DNA of EBV.

A

Linear dsDNA molecule of about 175kbp

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12
Q

Describe the structure of EBV.

A

Icosahedral capsid.
100-110nm in diameter.
Contains 162 capsomeres with a hole running down the long axis.
An amorphous, sometimes asymmetric material that surrounds the caspid designated as the tegument.
An enevlope containing viral glycoprotein spikes on its surface.

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13
Q

What is the main method of transmission for EBV?

A

Salivary contact

e.g. kissing, sharing food, babies toys, coughing.

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14
Q

At what age are the two peaks of infection seen in developed countries?

A

Ages 1-6 and 14-20

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15
Q

In developing countries, how many children are seropositive for EBV by the age of two?

A

90%

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16
Q

What percentage of teenagers or young adults with primary EBV infection get glandular fever?

A

30%

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17
Q

Which cells does EBV infect?

A

B-lymphocytes

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18
Q

What is the mechanism by which EBV infects B-lymphocytes?

A

By binding viral gp350 to CD21 and viral gp42 to MHCII.

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19
Q

In which area of the body can low grade virus replication and shedding be demonstrated in all seropositive individuals?

A

The epithelium of the pharynx.

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20
Q

What are the replication origins of the lytic and latent life cycles?

A

oriLyt and oriP

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21
Q

What happens immediately after viral binding?

A

Endocytosis and transport to the nucleus.

Genome circularises and is maintained as an extrachromosomal plasmid.

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22
Q

Which area of the body does EBV tend to be active in?

A

Nasopharyngeal lymphoid system (including tonsils)

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23
Q

How many B cells are persistently infected in asymptomatic carriers?

A

0.5-50 B cells/million

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24
Q

What is the major envelope protein of EBV?

A

Gp350

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25
Q

In the acute stage which cells control proliferative EBV infected cells?

A

NK cells
CD4
CD8

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26
Q

How many EBV genes are encoded during its latent phase?

A

About 11

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27
Q

Which nuclear antigens are encoded during the latent phase?

A

EBNAs 1, 2, 3A, 3B, 3C, and LP

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28
Q

Which latent membrane proteins are encoded during EBV’s latent phase?

A

LMP1, LMP2A, LMP2B

29
Q

What is the difference between LMP2A and LMP2B?

A

LMP2B uses an internal promoter and is N-terminally truncated compared to A.

30
Q

What is a BART?

A

BamHI A rightward transcript

They include several microRNAs

31
Q

What is the function of EBNA-1?

A

Maintenance of EBV episome.

32
Q

Which genes up-regulate B cell proteins?

A

LMP-1, EBNA-2, EBNA-3

33
Q

What is the function of LMP-2?

A

Protection of reactivation from latency.

34
Q

Which genes cause apoptosis?

A

BHRF1 and LMP1

35
Q

What effect can EBNA1 have in cancer?

A

It can activate potential oncogenes or inhibit tumour suppressor genes.

36
Q

What is the role of USP7?

A

It associated with p53, de-ubiquitinates and therefore inhibits its destruction.
i.e. USP7 stabilises p53

37
Q

What association does EBNA1 have with p53?

A

EBNA1 can associate with p53, blocking the ability of USP7 to associate and stabilise it, resulting in either mutations or degradation of p53.

38
Q

Where is CD40 found?

A

On germinal centre B cells.

39
Q

What allows B cells to switch Ig isotype and/or become a memory B cell?

A

Binding to CD40L (or CD154).

40
Q

What results in NFkappaB expression?

A

Downstream signalling via TRAF-binding domains.

41
Q

What do LMP1 and LMP2 mimic?

A

Normal B-cell survival signals to allow the viral infected cell to persist.

42
Q

Which EBV genes are expressed in Burkitt’s lymphoma?

A

EBER, EBNA-1, BART

43
Q

Which EBV genes are expressed in nasopharyngeal carcinoma and Hodgkin’s lymphoma?

A

EBER, EBNA-1 LMP-1, LMP-2, BART

44
Q

Which EBV genes are expressed in lymphoproliferative disease?

A

EBER, EBNA-1, EBNA-2, EBNA-3s, LMP-1, LMP-2, BART

45
Q

In which instances can lymphoproliferative lesions and lymphomas develop in EBV infected patients?

A

When the patient is immunocompromised.

46
Q

Where in the body might lymphoproliferative lesions and lymphomas develop?

A

GI tract or CNS

47
Q

Which diseases is EBV associated with in AIDS patients?

A

Oral leukoplakia and various non-Hodgkin’s lymphomas.

48
Q

Which condition accounts for half of the fatal cases of infectious mononucleosis?

A

Duncan X-linked lymphoproliferative syndrome.

49
Q

What are the risk factors for PTLD?

A
Degree of overall immunosuppression
EBV serostatus
Time post transplant
Recipient age
Ethnicity
50
Q

Is PTLD more common in children or adults?

A

Children

51
Q

Which transplants give a higher risk of developing PTLD?

A

Intestinal/multiorgan transplantation (11-33%)

52
Q

What is the clinical presentation of PTLD?

A

Fever
Lymphadenopathy
Allograft involvement
CNS symptoms

53
Q

How can PTLD be treated?

A
Reduction of immunsuppresion
Antiviral therapy
Monoclonal antibodies
Chemotherapy and radiotherapy
Interferon α
Surgical resection
Adoptive immunotherapy
54
Q

What is rituximab?

A

An anti-CD20 monoclonal antibody.

55
Q

What are the survival rates for somebody with PTLD?

A

25-60%

56
Q

What is adoptive immunotherapy?

A

T-cells stimulated and clonally expanded ex-vivo using EBV transformed LCL.
This generates a panel of host derived EBV-specific cytotoxic T-cells.
Those with highest cytotoxic activity are then transfused back into the patient to try to prevent EBV-PTLD development.

57
Q

Which age range is Burkitt’s lymphoma most common in?

A

3-14 years

58
Q

Which regions have higher incidence of Burkitt’s lymphoma?

A

High malarial regions.

59
Q

Why is Burkitt’s lymphoma associated with malaria?

A

Malaria is thought to inhibit the T cell response to EBV from an early age.

60
Q

How does Burkitt’s lymphoma present?

A

As a rapidly growing tumour of the jaw, face or eye.

61
Q

How is Burkitt’s lymphoma treated?

A

Chemotherapy - responds well in 50-80% of cases.

62
Q

What is the association of EBV to endemic Burkitt’s lymphoma?

A

95%

63
Q

What is the association of EBV to sporadic Burkitt’s lymphoma?

A

20-30%

64
Q

What is the name of the EBV expression pattern found in Burkitt’s lymphoma?

A

Latency I

65
Q

Which chromosomal translocation is found in all BL tumours?

A

All BL tumours harbour a chromosomal translocation that takes the oncogene c-myc (chromosome 8) to an immunoglobulin locus (chromosomes 14, 2 or 22) resulting in deregulated c-myc expression

66
Q

In Hodgkin’s lymphoma what percentage of the tumour mass is made up of malignant cells?

A

1-2%

67
Q

What is the name given to the EBV expression pattern found in Hodgkin’s lymphoma?

A

Latency II

68
Q

How is a nasopharyngeal carcinoma (NPC) treated?

A

Radiation therapy

Chemotherapy

69
Q

Which populations is NPC common in?

A

Southern chinese
Arctic
African mediterranean