CMV, EBV, & KSHV Flashcards

1
Q

EBV, CMV and KSHV are all?

A

Herpes viruses.

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2
Q

What is is the Genomic structure of KSHV, CMV, and EBV?

A

Double Stranded DNA.

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3
Q

What is the structure of these viruses?

A

Each has an icosahedral core surrounded by a lipoprotein envelope

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4
Q

Where does replication of these viruses take place?

A

The genome is replicated and viruses assembled in the nucleus in the nucleus

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5
Q

What type of infections do these bugs produce?

A

Self-limiting infections

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6
Q

What are some of the possible complications from these bugs?

A

Life threatening infections or cancers can occur especially in immuno-compromised patients

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7
Q

What kind of replication do herpes viruses undergo?

A

Lytic replication in a variety of cell types.

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8
Q

What is important about the primary infection of these herpes viruses?

A

The primary infection is usually asymptomatic

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9
Q

How do the viruses invade a host cell?

A

Attachment and penetration happens via virus glycoprotein-mediated fusion of envelope and plasma membrane

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10
Q

How does the released nucleocapsid migrate to the nuclear envelope of the host cell?

A

Via microtubules

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11
Q

What are the (IE) Immediate Early genes?

A

Virus specific transcription factors.

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12
Q

What is the function of the Immediate early genes?

A
  1. Use host RNA Polymerase II

2. STimulate transcription at virus early promoters

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13
Q

What are early genes?

A

Genes expressed after IE genes that encode many nonstructural proteins and enzymes.

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14
Q

What is the function of the early genes?

A
  1. The generate DNA replication machinery including viral DNA polymerase
  2. Generate Thymidine kinase (tk) which phosphorylates a variety of nucleotides besides thymidine
  3. Encode many nonstructural proteins
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15
Q

What are the functions of late genes?

A
  1. Encode structural proteins (capsids & Glycoproteins)
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16
Q

What is the cause of syncytia formation?

A

Viral encoded glycoproteins

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17
Q

Where does virus assembly occur?

A

In the nucleus, nucleocapsids bud first into the perinuclear space

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18
Q

As an alternative to lytic infection what do all herpes viruses undergo?

A

Latency.

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19
Q

What happens to Herpes viruses during latency?

A

Entire viral genome is maintained extrachromosomally in the host but no virus particles are produced.

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20
Q

What are the three stages of latency?

A
  1. Establishment
  2. Maintenance
  3. Reactivation
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21
Q

Under what circumstances does reactivation occur?

A
  1. Lapse in immunity (AIDS=KSHV)
  2. Stress
  3. Sunlight
  4. Menstration
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22
Q

What are the Betaherpesvirnae?

A
  1. CMV
  2. HHV-6
  3. HHV-7
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23
Q

What are the Gammaherpesvirinae?

A
  1. EBV

2. HHV-8

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24
Q

How are the Betaherpesvirnae and Gammaherpesvirinae different from Alphaherpesvirinae?

A

More isidious (less aggressive)

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25
Q

Is CMV highly contagious?

A

No

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26
Q

What is a huge determining factor in the age at which one may be infected with CMV?

A

Socioeconomic status. (THE LOWER THE STATUS THE EARLY ONE TENDS TO BE INFECTED)

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27
Q

Where is CMV usually found?

A

Saliva, urine, breast milk, semen, cervical secretions,blood, and transplanted organs

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28
Q

Who are the most at risk populations?

A

Neonates, Gay men, day care workers, pregnant workers, immunocompromised patients

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29
Q

How is infection of CMV spread?

A

Through direct contact with secretions, NOT BY AEROSOL

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30
Q

Where does primary replication of CMV take place?

A

Epithelial cells followed by spread to lymphoid tissue

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31
Q

What cells does CMV latently infect?

A

B-cells, T-cells, monocytes, and lymphocytes.

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32
Q

What is a common characteristic of CMV infected cells?

A

CMV causes Large puffed up cells

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33
Q

What are the symptoms of neonatal in utero infections by CMV?

A

Usually asymptomatic but can result in retardation and deafness

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34
Q

What are the symptoms of adult infection?

A

Mostly asymptomatic but mononucleosis accompanied by fever can occur

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35
Q

What subset of patients are particular at risk?

A

Immunocompromised

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36
Q

What do most organ transplant patients get?

A

CMV infection with pneumonitis representing the most life threatening aspect

37
Q

What are the 2 ways in which organ transplants lead to CMV infection?

A
  1. CMV from donor

2. Reactivation of CMV in recipient

38
Q

What is a promising prophylactic regiment for organ transplant in relation to CMV?

A

1.ANti CMV Ig + Ganciclovir

39
Q

What perticular complications from CMV is seen mostly in AIDS patients?

A

Primarily Retinitis but also colitis and pneumonitis.

40
Q

How is a diagnosis of CMV made?

A
  1. ELISA or PCR detection

2. Shell vial assay uses immunofluorescence to detect an immediate early protein after 24H of cell culture infection

41
Q

What is the treatment for CMV

A

Ganciclovir and the prodrug Valaganciclovir

42
Q

What is Ganciclovir?

A

A guanosine analog similar to acyclovir

43
Q

What drug is used in Ganciclovir resistant infections?

A

Foscarnet.

44
Q

Is there a vaccine against CMV?

A

NO

45
Q

What else is Foscarnet used to treat in relation to CMV?

A

Retinitis in AIDS patients

46
Q

What is the predominant factor determining age of infection by EBV?

A

Socioeconomic status

47
Q

What is the usually outcome of EBV infection in adolescence and early adulthood?

A

Infectious Mononucleosis

48
Q

What percentage of the adult population contains the antibody to EBV?

A

90-95%

49
Q

What can else can EBV cause in immunocompromised patients?

A

Oral Hairy LEUKOPLAKIA

50
Q

What is OHL?

A

OHL usually develops when CD4 counts are <400 and is characterized by white hairlike projections arising from the side of the tongue (differentiated from Candidal thrush because OHL will not rub off with a tongue blade)

51
Q

What disease is seen in transplant patients infected with EBV?

A

Posttransplant lymphoproliferative disease (PTLD)

52
Q

What two Neoplasias are associated with EBV?

A

Burkitt’s lymphoma, Nasopharyngeal carcinoma

53
Q

What is the primary way that EBV is spread?

A

Sucking faces (kissing saliva)

54
Q

What is the incubation period for EBV?

A

4 to 7 weeks

55
Q

Where does the initial viral replication take place in EBV infection?

A

Oropharyngeal epithelium

56
Q

Where is the secondary site of infecttion in EBV?

A

Lymphoctes, spleen, then Liver

57
Q

Where does EBV remain latent?

A

B-cells and throat epithelium

58
Q

What occurs for many weeks during EBV infection?

A

Oral shedding

59
Q

What are the symptoms of EBV infection?

A

1.Most infections are asymptomatic

60
Q

What are the symptoms of Infectious Mononucleosis?

A
  1. Sore Throat
  2. Fever
  3. malaise
  4. lymphadenopathy
61
Q

How does one arrive at a diagnosis of Infectious mononucleosis?

A

1.At least 50% atypical large lymphocytes with lobulated nuclei

62
Q

What are these large lymphocytes?

A

T-Cells responding to the infection, NOT INFECTED B_CELLS

63
Q

What are the antigenic markers for EBV?

A
  1. EBNA-EBV nuclear antigens arise early in primary infection
    - Conversion to anti-EBNA IgG indicates resolution of primary infection
  2. VCA - Viral capsid antigen
    - Anti-VCA IgM indicates primary infection
    - Anti-VCA IgG without anti-EBNA IgG indicates primary infection
    - Anti-VCA IgG without anti-EBNA IgG indicates past infection
  3. EA-early antigen is detected in cells that do not produce virus
64
Q

What is the most commonly used tool to confirm a diagnosis of EBV infectious mononucleosis?

A

Test for heterophile antibodies (Monospot test)

  • These antibodies agglutinate sheep red blood cells
  • Not present in all patients, origin not understood
  • Distinguishes EBV mono from CMV mono
65
Q

What is the treatment for EBV Mono?

A

Supportive care

With hold athletes due to possible inflammation of the spleen

66
Q

What is the treatment for Oral leukoplakia?

A

Acyclovir

67
Q

What is PTLD?

A

Uncontrolled proliferation of B-Cells due to their transformation by EBV and the absence of CTLs to control them

68
Q

What patients are at highest risk?

A

Highest risk is in seronegative transplant recipents in the first year

69
Q

What is the treatment for PTLD?

A

Stop Immunosuppression

  • but monitor closely for rejection
  • Acylovir not helpful because the virus is latent and not reproducing
70
Q

What is Burkitt’s Lymphoma?

A

Neoplasm of B-Cells that affects bones of the Jaw

-endemic in central Africa and New Guinea

71
Q

What are the three factors associated with Burkitt’s?

A
  1. Early EBV infection leading to latency
  2. Activation of C-MYC
  3. Malaria
72
Q

What is the cure rate with early detection of Burkitt’s?

A

80%

73
Q

What is Nasopharyngeal carcinoma?

A
  1. Neoplasm of epithelial cells
  2. Associated with EBV world wide
  3. High frequency in Southern China-High salt diet cofactor
74
Q

What is the initial presentation of Nasopharyngeal carcinoma?

A

Painless lump in neck

75
Q

What is the survival rate for Nasopharyngeal carcinoma

A

At best 60% survive past 10 years

76
Q

How is HHV-8 related Karposi’s sarcoma?

A

It is neccesary but not sufficient

77
Q

Where does the latent virus reside in humans?

A

B-cell and endothelial cell latency tropism

78
Q

Where do KS tumors occur?

A

In the lining of the lymphatic system

79
Q

What happens to the lymphatic channels?

A

Fill with Bloodcells hence the bluish, bruised appearance of lesions

80
Q

In what populations is KS classically seen?

A

Mediterranean and Sub-saharan african (Not STD in these cases)

81
Q

What sub-population of patients in the US is KS most seen in?

A

AIDS patients

82
Q

How is the virus transmitted?

A

Sexually but virus not present in semen or vaginal secretions but present in Saliva

83
Q

What is the incubation period for KS?

A

10 years

84
Q

When is KS life threatening

A

If the patient is immunocompromised

85
Q

What must accompany infection for disease to be symptomatic

A

Loss of the immune system

86
Q

What is the treatment in AIDS patients?

A

Resection and chemotherapy against the tumor

87
Q

What 2 other B-Cell abnormalities is HHV-8 linked to?

A
  1. Primary effusion lymphoma

2. Castleman’s disease

88
Q

What is Primary effusion Lymphoma?

A
  1. Non Hodgkin’s B-cell lymphoma
  2. Commonly found in body cavities
  3. mean survival time is 2-6 months
  4. KSHV found in virtually all tumors of HIV + patients
89
Q

What is Catleman’s disease?

A
  1. Lymph node tumors, not strictly a cancer

2. KSHV found in essentially all tumors of HIV + patients