14 - Viral oncogenicity

Question 1

Onciogenic effect

Answer 1

• Cell proliferation (=rapid increase)
• Less differentiated cell forms (“ancient”)
• Less effective cell forms
• Usually not able to function effectively

→ Tumors

Question 2

Cellular oncogenesis

Answer 2

• Oncogenes (even 5% of the genome)
• Genes necessary for cell division and maturation
• In the active cell suppressed proto-oncogens (c-onc)
• Activation - oncogenesis

Question 3

Oncogenic viruses

Answer 3

• DNA viruses:
  
  • Papillomaviridae
  • Polyomaviridae
  • Adenoviridae
  • Herpesviridae
  • Poxviridae
  • Hepadnaviridae
• RNA viruses:
  
  • Retroviridae

Question 4

Types of tumors

Answer 4

1. ​Benignant:
   
   • ​Limited
   • Less invasive
   • Less destructive
2. Malignant:
   
   • ​Invasive
   • Destructive

Question 5

Mechanisism of viral oncogenesis

Answer 5

• Activation of cellular oncogenes:
  
  • ​Retroviridae (avian leukosis virus, feline leukosis virus)
  • DNA integration into the cellular genome
  • Near by c-onc genes
  • Retroviral LTR regions → intesive promotor - translation

→ c-onc activated – oncoprotein expression - cell proliferation

→slow developing lymphatic tumors (leukemias)

• Expression of viral oncogenes:
  
  • Retroviridae (Avian sarcoma virus, Feline sarcoma virus)
  • Recombination between the cellular and proviral genome
  • Transposition of the c-onc gene into the virus genome → v-onc!
  • The oncogene is carried by the virion
  • After infection quick oncoprotein production
  • Fast developing malignant tumors (sarcoma, carcinoma)
  • The v-onc gene is not essential for the virus
  • Replacing essential genes (envelope protein gene)
  • Defective particles – envelope from leukosis viruses
• Viral proteins with consequent oncogenic effect:
  
  • Oncogenic DNA viruses
  • Viral modulator proteins control the cell machinery
  • Inactivation of cellular anti-oncogenic proteins
  • Inhibition of the apoptosis (Adenoviridae)
  • Usually benignant tumors
• In vitro cell cultures: malignant transformation
  
  • Contact inhibition is terminated: microtumors