Lec 16 - Oncogenic viruses Flashcards

1
Q

List the features of transformation.

A
  • Uncontrolled growth
  • No contact inhibition = cells grow on top of each other
  • No anchoring dependence
  • Form colonies on semi-solid media
  • Altered GF and nutrient requirements = don’t need as much
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2
Q

What is carcinogenesis?

A

Complex multistage process by which cancer develops

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3
Q

What is cancer?

A
  • Group of diseases caused by abnormal cell growth
  • Potential to metastasise = interferes with normal organ function
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4
Q

What is a tumour?

A

Swelling from abnormal growth of tissue

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5
Q

What is the difference between benign and malignant cancers?

A

Benign = restricted to 1 site
Malignant = uncontrolled growth with invasion and metastasis by blood and/or lymph

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6
Q

Where does each of the following types of cancer originate from?
- Carcinoma
- Sarcoma
- Leukaemia
- Lymphoma and multiple myeloma
- CNS cancer

A
  • Carcinoma = skin/epithelia
  • Sarcoma = connective tissue
  • Leukaemia = blood forming tissue ie bone marrow
  • Lymphoma and multiple myeloma = immune cells
  • CNS cancer = brain and spinal cord
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7
Q

What is metastasis?

A

Secondary growth at a distance from primary cancer site

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8
Q

What percentage of human cancers do viruses cause and what cancers?

A

20%
Liver and cervical cancers

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9
Q

What cancers do the following viruses cause?
- Epstein Barr virus
- HBV
- Human T lymphotropic virus 1
- Human papillomavirus
- HCV
- Kaposi sarcoma associated herpesvirus
- Merkel cell polyomavirus

A
  • Epstein Barr virus = Hodgkin and Burkitt lymphomas, carcinoma, sarcoma
  • HBV = hepatocellular carcinoma
  • Human T lymphotropic virus 1 = T cell leukaemia
  • Human papillomavirus (HPV) = hepatocellular carcinoma, lymphoma, squamous cell carcinoma (cervical)
  • HCV - hepatocellular carcinoma, lymphoma
  • Kaposi sarcoma associated herpesvirus = Kaposi sarcoma, lymphoma
  • Merkel cell polyomavirus = Merkel cell carcinoma (skin)
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10
Q

What is the difference between RNA and DNA viruses in how they activate the cell cycle?

A

RNA viruses = encoded oncogenes to activate growth signalling pathways
DNA viruses = have tumour suppressor proteins to disrupt inhibitory pathways for proliferation

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11
Q

What are proto-oncogenes and oncogenes?

A
  • Proto-oncogenes = normal cellular proteins promoting regulation and proliferation of normal cells
  • Oncogenes = mutated proto-oncogene allowing uncontrolled growth
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12
Q

How do oncogenes and tumour suppressor genes induce abnormal cell growth? How many mutations are needed for each and what type of functional mutation is involved with each?

A
  • Oncogenes = recessive (1 copy) gain of function stimulating proliferation
  • Tumour suppressors = dominant (2 copies) loss of function allowing proliferation
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13
Q

How do retroviruses convert proto-oncogenes to oncogenes?

A

Integration of viral genome

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14
Q

What 2 processes do retroviruses use to induce transformation? Describe each.

A
  1. Acutely transforming retrovirus = tumour in weeks; incorporates host genome into viral genome to make oncogenes then integrate oncogene into next cell
  2. Slowly transforming retrovirus = tumour in months; integrates promoter into host genome’s proto-oncogene to convert it to oncogene
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15
Q

What step in the HIV replication cycle - or any retrovirus replication cycle - causes transformation?

A

When viral integrase inserts cDNA into host genome

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16
Q

What is Rous sarcoma virus (RSV) and how does it induce transformation?

A
  • Chicken virus from altered Avian leukosis virus (ALV) by having polyprotein with src added to it
  • src = tyrosine kinase which binds activated GF receptor and sends proliferation signal when phosphorylated
  • Cellular c-src = C-terminal region to inhibit proliferation when phosphorylated
  • Viral v-src = no C-terminal region = constitutive proliferation
17
Q

What are the 2 types of oncogene retroviruses?

A
  1. Oncogene transducing retroviruses = oncogene in genome; causes transformation and rapid cancer
  2. Oncogene deficient retroviruses = insert LTR to overexpress proto-oncogene; slow and minority cancer
18
Q

What cancers does Human T cell lymphotropic virus type 1 (HTLV-1) cause and how?

A

Adult cutaneous T cell lymphoma (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
Viral proteins unique to virus (no cell homologues)
1. Tax = activates host genes that promote proliferation and inhibit apoptosis; starts oncogenesis
2. HBZ = binds pRB to promote progression thru cell cycle; maintains oncogenesis

19
Q

How do DNA viruses contribute to oncogenesis? What cellular protein do they interact with?

A

Induce S phase for viral replication; interfere with tumour suppressor Rb protein

20
Q

How does HCV interact with Rb?

A
  1. NS5B viral protein interacts with Rb in cytoplasm
  2. Recruits E6AP E3 ubiquitin ligase to mark RB for degradation in proteosome
21
Q

What is the function of p53 and why do many viruses target it?

A

Tumour suppressor that arrests cell cycle after DNA damage then induces apoptosis if needed.
Virus infection causes DNA damage, so viruses alter p53 to avoid apoptosis.

22
Q

How does SV40, HPV and adenovirus target p53? Why do they have a similar effect despite different methods?

A
  1. SV40 = large T antigen stabilises p53 in inactive state
  2. HPV = E6 protein triggers degradation of p53
  3. Adenovirus = E18 protein blocks transcription activation function of p53
    All have similar effect bc Rb’s binding site is matched to a degree by all 3 viruses