9b- EBV

Question 1

What are the EBV associated neoplasms?

Answer 1

• lymphomas
  
  • endemic Burkitt lymphoma
  • post-transplant lymphoma
  • extranodal NK/T cell lymphoma (nasal type)
• nasopharyngeal carcinoma

Question 2

Describe the major EBV virion features

Answer 2

• gammaherpesvirus
  
  • all herpes viruses (including EBV) have 2 life cycles; lytic replication and latency
• large double stranded DNA genome
• enveloped (labile in the environment)

Question 3

Describe the lytic replication cycle

Answer 3

1. virus binds and fuses to host cell membrane
2. viral DNA transported to nucleus
3. viral DNA circularizes and associates with histones (to look more like host DNA)
4. alpha/beta/gamma genes expressed
5. viral DNA packaged into capsid and released

Question 4

What are the main roles of alpha, beta, and gamma genes in lytic replication?

Answer 4

• alpha gene products transactivate transcription of beta genes
• beta gene products are required for DNA synthesis
• gamma gene products are structural components of the virion

Question 5

Describe the mechanism of EBV latent infection and its reactivation

Answer 5

1. same infection steps as lytic replication
2. histone-associated viral DNA instead becomes latent however, with little to no expression
3. EBV reactivation from B cells is triggered by B cell differentiation into plasma cells (reactivation mechanism not understood)
4. poorly controlled reactivation is a significant risk factor for EBV-driven malignancies

Question 6

Why do most EBV-associated lymphomas have germinal center markers?

Answer 6

Because most lymphomas arise from B cells within the germinal center (undergoing proliferation and differentiation)

Question 7

How does infection with EBV differ by age?

Answer 7

• EBV acquired in the first decade of life leads to mild cold-like symptoms
  
  • in developing countries >95% of kids are infected by 3 years old
  • in developed countries ~70% of 12 year olds are EBV positive
• EBV acquired in adolescence and beyond leads to acute infectious mononucleosis

Question 8

What are the characteristics of infectious mononucleosis?

Answer 8

• massive CD8+ T cell expansion (Downey cells)
• significant increase in activated B cells (very few EBV infected)
  
  • leads to transient increase in Ab production
  • basis for the heterophile mono spot test

Question 9

What are the symptoms of infectious mononucelosis?

Answer 9

• symptoms:
  
  • fever
  • lymphadenopathy/hepatosplenomegaly
  • pharyngitis
  • malaise and fatigue
  • virus in saliva
• lab data:
  
  • atypical lymphocytes
  • heterophile antibody titer

Question 10

What are the proposed mechanisms of viral oncogenesis?

Answer 10

Question 11

What evidence is there against the theory of direct transformation?

Answer 11

• the historical theory was the expression of EBV latency proteins is necessary for oncogenesis
• recently, it has been showed not only that latency proteins are NOT necessary but lytic proteins MAY be necessary for oncogenesis