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Virology > Lecture 28 - Oncogenic Viruses > Flashcards

Lecture 28 - Oncogenic Viruses Flashcards

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1
Q

Three classes of cancer-causing agents

A

1) Chemical carcinogens
2) UV and ionising radiation
3) Viruses

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2
Q

Carcinoma

A

Tumour of epithelial origin

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3
Q

Sarcoma

A

Tumour of fibroblasts

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4
Q

Tumours of leukocyte origin

A

Lymphoma (when solid)

Leukaemia (when circulating)

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5
Q

Are most cancers mono- or polyclonal?

A

Monoclonal

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6
Q

Some characteristics of transformed cells
1)
2)
3)

A

1) Lack of contact inhibition of growth
2) Lack of dependence on exogenous growth factors
3) Lack of anchorage dependence on some cell types

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7
Q

What happens in G1?

A

Synthesis of proteins required for DNA synthesis

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8
Q

When is DNA replicated?

A

S phase

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9
Q

What happens in G2 phase?

A

Synthesis of proteins for daughter cells

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10
Q

When is the restriction point in the cell cycle?

A

G1

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11
Q

What determines whether a cell stops at, or progresses beyond the restriction point in the cell cycle?

A

Environmental cues

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12
Q

C-onc

A

Cellular oncogenes or proto-oncogenes

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13
Q

V-onc

A

Viral-oncogenes.

Can be a host oncogene, modified host oncogene, or a novel viral protein

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14
Q

Examples of tumour suppressor genes

A

Retinoblastoma, p53

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15
Q

Four main classes of oncogene

A

1) Growth factors
2) Growth factor receptors
3) Intracellular signal transducers
4) Transcription factors

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16
Q

20% of human cancers are associated with what?

A 
Human T cell leukaemia virus type 1
Hepatitis C virus
Human papilloma virus
Epstein-Barr virus
Hepatitis B virus
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17
Q

RNA viruses associated with human cancers

A

Human T cell leukaemia virus type 1 (retrovirus)

Hepatitis C virus (flavivirus)

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18
Q

DNA viruses associated with human cancers

A

Human papilloma virus (papovavirus)
Epstein-Barr virus (herpesvirus)
Hepatitis B virus (hepadnavirus)

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19
Q

Are retroviruses lytic?

A

No

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20
Q

If a retrovirus carries an oncogene, what type is it?

A

V-onc that has a C-onc counterpart

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21
Q

What does retroviral transformation often involve?

A

Stimulating activators of cell cycle

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22
Q

Are oncogenic DNA viruses lytic?

A

Yes, normally

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23
Q

Type of V-onc often carried by DNA viruses

A

A unique viral product. No C-onc

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24
Q

What does DNA viral transformation often involve?

A

Inactivation of cell-cycle inhibitors

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25
Two types of oncogenic retroviruses
Endogenous and exogenous
26
Normal retroviral proviral genome
LTRs flanking gag, env, pol
27
Defective oncogenic retroviral genome
LTRs flanking gag, env, pol, but an oncogene is disrupting one of the gag, env or pol
28
Replication-competent oncogenic retroviral proviral genome
LTRs flanking gag, env, pol, with an oncogene that isn't disrupting gag, env or pol
29
Example of a replication-competent oncogenic retrovirus
Rous sarcoma virus
30
Three mechanisms of tumour production by exogenous retroviruses
1) Transducing (acute transforming) 2) Cis-activating (non-acute transforming) 3) Trans-activating
31
Transducing retroviruses
Introduce a v-onc gene under LTR transcriptional control into host genome
32
Cis-activating retroviruses
Insertional mutagenesis. | Doesn't carry a v-onc gene, but upon integration LTR drives expression of a C-onc gene
33
Trans-activating retroviruses
Contains a gene-regulation protein that drives tumour growth
34
Type of tumours produced by transducing retroviruses
Polyclonal
35
State of most transducing retroviruses
Replication defective. | Except for Rous sarcoma virus
36
Are transducing retroviruses found in humans?
No. Rous sarcoma virus is a virus of chickens
37
How can insertional mutagenesis drive tumour growth? 1) 2)
Either: 1) Proviral LTR can act as a promoter for c-onc in cis with provirus. 2) Provirus unwinds DNA upstream of c-onc, acts as a transcriptional enhancer
38
Best-studied cis-acting retrovirus
Murine leukaemia virus
39
Examples of cis-acting retroviruses
Murine leukaemia virus | Koala retrovirus
40
Example of a trans-acting retrovirus
Human T-cell lymphotropic virus type 1 (HTLV-1)
41
What is human T-cell lymphotropic virus type 1 associated with?
Adult T-cell leukaemia-lymphoma
42
How is human T-cell lymphotropic virus type 1 transmitted?
Placenta, breast feeding, sexual intercourse, contaminated needles
43
Effects of human T-cell lymphotropic virus
Virus persists for life, often causing no disease. | After 20-40 years, a small proportion of those infected develop adult T-cell leukaemia-lymphoma
44
What does HTLV infect?
CD4+ T cells
45
Regulatory proteins in HTLV
Tax, rex
46
Tax 1) 2) 3)
1) Regulatory protein in human T-cell lymphotropic virus. 2) Transcription factor that acts on the LTR region, but also can act on C-onc genes in the host genome. 3) Also acts to upregulate IL-2, IL-2R transcription, to promote T cell proliferation
47
HTLV protein involved in oncogenesis
Tax
48
Why do some DNA viruses lead to oncogenesis?
Need host cell to be in S phase so that genomes can be replicated. Most cells are in G0 or G1. Early proteins are normally encoded to get host cell into S phase
49
Features of DNA stimulated tumours 1) 2) 3)
1) Limited viral protein expression. 2) Early gene expression 3) Can show integration of viral genome or episome
50
Function of retinoblastoma susceptibility gene
Controls transition from G1 to S. In hypophosphorylated active form sequesters E2F family of transcription factors, preventing them from driving the cell cycle forward
51
Function of p53
Transcription factor that induces expression of proteins that arrest cell growth and initiate apoptosis in response to DNA damage
52
Proportion of human tumours that have a mutation in the p53 gene
50%
53
Examples of viral strategies for suppressing p53 function 1) 2)
1) Hep C binds a protein to p53, prevents nuclear localisation 2) Papilloma viruses mark p53 for degradation
54
HPV seotypes that lead to carcinoma
HPV-16 and -18
55
HPV E6 protein
Marks p53 for degradation
56
HPV E7 protein
Inhibits retinoblastoma susceptibility protein
57
What happens in papillomavirus oncogenesis?
HPV is randomly integrated into host genome. E2 protein is lost, which normally negatively represses E6 and E7 proteins
58
Type of cancer linked to hep B
Hepatocellular carcinoma
59
Proportion of those infected with hep B that develop hepatocellular carcinoma
2-10% of patients
60
How does hep B lead to hepatocellular carcinoma? 1) 2)
1) Random integration of episome into host genome. Transactivating gene X can deregulate a nearby C-onc (src tyrosine kinase). 2) Repeated destruction and regeneration of hepatocytes can lead to accumulation of mutations
61
Increase in hepatocellular carcinoma risk when infected with hep C
100x increase in risk
62
``` Cancers associated with EBV 1) 2) 3) 4) ```
1) Burkitt's lymphoma (Africa) 2) Nasopharangeal cancer (common in China, SE Asia) 3) B cell lymphomas in immunosuppressed patients (EG: AIDS patients) 4) Detected in ~40% of Hodgkin's lymphoma patients
63
Burkitt's lymphoma genesis
Translocation of C-myc (chromosome 8) to a part of chromosome 14 which is under transcriptional control of a promotor for Ig heavy chain production
64
Role of EBV in Burkitt's lymphoma
EBV transforms B cells, leading to uncontrolled expansion. | Enhances effects of mutations such as C-myc translocation from Chr.8 to Chr.14

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