CMV, EBV, KSHV (HHV-8) Flashcards

1
Q

What type of virus are CMV, EBV, and KSHV?
• What do they share a common tropism for?
• Which of these cause cancer?

A

All are herpes Viruses

  • All share tropism for Lymphocytes
  • EBV and KSHV are oncogenic
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2
Q
Describe the following structural features of the Herpes virus? 
• Genome Structure
• Capsid style
• Enveloped
• Where does virus assembly take place?
A

Genome:
• Linear dsDNA (150-250 kbp)

Capsid:
• Icosahedral Capsid
• Enveloped

REPLICATION AND ASSEMBLY TAKE PLACE INSIDE THE HOST CELL NUCLEUS

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3
Q

Which of the herpes viruses is the largest?

A

CMV is the largest

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4
Q

What is the Tegument?

• what is found here?

A

Tegument:
• Found Between the envelope and capsid

What does it contain:
•number of proteins needed to infect the cell and shut down host cell synthesis of normal proteins to produce viral proteins

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5
Q

Which of the following are Beta and which are Gamma herpes viruses?

A

Beta = CMV

Gamma = EBV, HHV-8 (KSHV)

**Note: EBV and HHV-8 can cause cancers

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6
Q

What is unique about the structure of the herpes virus linear genome structure for:
• CMV
• EBV

A

• Line is divided into Long Segement and Short segment

CMV:
• Flanking each of these segments is two pairs of genes that are the same but run in opposite directions

EBC:
• Internal Repeats separate Long and short segment

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7
Q

T or F: herpes viruses can take part in a lytic cycle OR stay in a latent phase.

A

TRUE, the latent phase is what makes herpes life-long

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8
Q

Describe the Steps in the Lytic Cycle for Herpes viruses.

A

ENVELOPE fuses with cell and NUCLEOCAPSID rides microtubules to host nuc.

Immediate Early Phase
• Early Transciption Factors - redirect host RNA pols. to make viral genes

Early Phase
• HERPES own DNA pols replicates Genome

Late Phase
• Packing into capsid occurs in the nucleus

Assembled Virus Buds from the Nucleus and out of the cell

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9
Q

What events occur if the herpes virus decides to undergo a latent phase rather than lytic?

A
  • NO VIRAL PARTICLES are PRODUCED
  • Entire Genome is Maintained Extrachromosomally
  • FEW viral genes are expressed
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10
Q

What are the 3 phases of latency?

• What causes the final stage?

A

Establishment

Maintenance

Reactivation - Due to a Loss in Host Immune Response

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11
Q

T or F: latency in herpes viruses causes the infection to be LIFE-LONG

A

True

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12
Q

What 4 drugs are most often used to treat Herpes viruses?

• Which are 1st line and which are 2nd line?

A

4 Drugs:
1st line (pro-drugs)
• Acyclovir
• Ganciclovir

2nd line (not pro-drugs) 
• Foscarnet
• Cidofovir
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13
Q

Acyclovir

MOA

A
  • PRODRUG is phosphorylated FIRST by HERPES Thymidine Kinase (two more phosphorylations occur by host kinases)
  • Is Preferentially used by HERPES DNA pols.

(thymidine analogue)

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14
Q

Which of the herpes drugs is most often used to treat CMV infections?

A

Ganciclovir

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15
Q

Foscarnet

MOA

A
  • Blocks Pyrophosphate Release (aka cleaving of the P-P bond)
  • NOT a prodrug and DOES NOT REQUIRE activation
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16
Q

Cidofovir

MOA

A

Cytidine analogue (doesn’t need to be activated)

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17
Q

Why can’t anti-herpetic drugs cure herpes?

A

They ONLY affect herpes in its active Relicating state and have no effect on the lytic state

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18
Q

T or F: CMV is not highly contagious , that’s why rates of CMV infection are generally very low in society.

A

FALSE, while it IS true that CMV is not highly infectious is it however VERY PREVALENT with 50-80% of adults being affected.

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19
Q

T or F: Like HSV-1 both CMV and EBV are sexually transmitted.

A

False, CMV IS sexually transmitted while EBV is NOT (despite its reputation)

20
Q

What is the PRIMARY (first) site of replication for CMV?
• Secondary?
• Latency?

A

Primary:
Epithelial Cells

Secondary:
• Spreads through Lymphoid Tissue

Latency:
• Hangs out in B and T cells and Monocytes

21
Q

Compare and contrast Childhood infections of CMV with those that occur as an adult?

A

Childhood:
• Mostly Asymptomatic

Adulthood:
• can result in mononucleosis with fever

22
Q

How does CMV affect Neonates?

• How many are affected in utero?

A
  • In utero CMV in 1% of U.S. births

* Asymptomatic 90% of the time but CAN cause Deafness and Mental Retardation

23
Q

What groups of people are at the highest risk of getting CMV infection?

A
  • Immunocompromised (TRANSPLANT patients)
  • Day Care Workers
  • Pregnant Workers
  • Gay Men
24
Q

When you think transplant patient, think CMV!

A

When you think transplant patient, think CMV!

25
Q

T or F: most transplant patients will develop a CMV infection.

A

True, but not all will cause disease

26
Q

How does CMV exposure occur in transplant patients?

• How would you treat someone who is at high risk for CMV exposure during transplant?

A
  • CMV+ organ is recieved OR
  • REACTIVATION of latent CMV in CMV+ pt.

• HIGH RISK (seropositive) pts. are given PROphylactic Ganciclovir and CMV Ig

27
Q

How do you diagnose and treat someone with a CMV infection?

• 1st and 2nd line treatment

A

Dx:
• Detection of VERY Large Lymphocytes
• ELISA, PCR, Shell Vial Assay

Treatment:
1st line
• Ganciclovir

2nd line
• Foscarnet
• Cidofovir

28
Q

What is a shell vial assay?

A

• Uses Antibody to detect Immediate Early Proteins

this is quicker because you don’t have to wait for the virus to completely replicate

29
Q

What two cancers can be caused by EBV?

A
  • Burkitt’s Lymphoma

* Nasopharyngeal Carcinoma

30
Q

Which causes hairy leukoplakia of the tongue: EBV or CMV?

A

EBV

31
Q

Where is the primary site of replication for EBV?
• Secondary?
• Tertiary?

A

Primary - Epithelium

Secondary - Lymph Nodes

Tertiary - Liver and Spleen

32
Q

Why do people often not know they are infected with EBV and thus spread it to other people?

A

EBV remains latent in throat epithelia and B cells and there can be oral shedding for weeks

33
Q

What some of the key symptoms of Infectious Mononucleosis (EBV) infection?

A
  • Sore Throat
  • Fever 1-2 wks
  • Malaise
  • Lymphadenopathy
  • Uneventful Recovery
34
Q

What patients present with hairy leukoplakia?

• what causes it?

A

AIDS patients are really the only people this is seen in

• Caused by EBV

35
Q

How is EBV typically diagnosed?

A
  • Symptoms
  • Greater than 50% atypical, LARGE lymphocytes
  • Monospot test (specific but not sensitive)
  • EBNA and VCA antigens
36
Q

How does the monospot test work?

• How good is this test at catching EBV?

A

HETEROPHILE antibodies agglutinate Sheep RBCs

• on 1/2 of people infected with EBV ever produce ant-sheep antibody

37
Q

*What are EBNA and VCA?

A

EBNA (EB Nuclear Antigens)
• Immediate Early proteins that Assist in transcription and Genome Replication

VCA (Virus Capsid Antigen)
• Produced during Lytic Replication

38
Q

*How are EBNA and VCA used to stage an EBV infection?

A

Anti-VCA rises before anti-EBNA therefore

Primary Infection
• Anti-VCA+ and anti-EBNA -

Prior Infection
• Anti-VCA+ and anti-EBNA+

39
Q

*What is posttransplant lymphoproliferative disease (PTLD)?
• which transplant pts. are at highest risk?
• What virus causes this?
• How do we treat?

A

PTLD
• B Cell lymphoma in Transplant Patients

Highest Risk:
• Patients in the 1st year of treatment who are SERONEGATIVE for EBV

Treatment:
• Stop Immunosuppression

40
Q

*Who typically gets Burkitt’s lymphoma?

• factors that play a role in getting the disease?

A

Young Children in Central Africa

Factors:
• Early EBV infection - causes immortalization leading to more replication and more mutations

  • c-MYC gets activated as a result of mutations
  • Superimposed Malaria infection suppresses normal immune response to EBV
41
Q

How curable is Burkitt’s lymphoma?

A

80% cure rate in cases that are detected early

42
Q

Which is more closely associated with EBV, Nasopharyngeal Carcinoma or Burkitts Lymphoma?

A

There is almost 100% association of Nasopharyngeal Carcinoma with EBV.

43
Q

Where is nasopharyngeal carcinoma most prevalent?

A

Southern China - thought to be tied in to high consumption of Nitrosamines and Grilled Fish in these areas

44
Q
Compare and Constrast EBV to CMV in terms of: 
• Cell in which it remains Latent
• Effect on Transplant Patients
• Transmission
• Mono-spot test 
• Oncogenesis
A

Latency:
• Occurs in B cells for Both

Effect on Transplant Patients:
• CMV - PNEUMONIA 1-4 months After transplant
• EBV - B cell lymphoma

Transmission:
Both transmit through fluids (enveloped virus)
• CMV - sexually transmitted
• EBV - only transmitted via Saliva

Monospot:
• CMV - ALWAYS negativ
• EBV - sometimes positive

Oncogenesis:
• only EBV causes cancer

45
Q

What are some diseases caused by HHV-8 (KSHV)?

A
  • Kaposi’s Sarcoma
  • Primary Effusion Lymphoma
  • Castleman’s disease