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6BBYI316 Viruses and Disease Semester 2 notes $8.38
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6BBYI316 Viruses and Disease Semester 2 notes

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Semenster two notes for the 6BBYI316 Viruses and Disease at King's College London. I got a first using these notes alongside the semester 1 notes. Note that these notes can be used for other courses/ universities.

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  • September 5, 2017
  • 60
  • 2017/2018
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Principles of viral oncogenesis (Lecture 10A)

Background
What is oncogenesis?
 Process that leads to development of cancer
 Mutations that affect pathways that control cell proliferation
 Mutations may be inherited or caused by DNA damage, environmental
carcinogens or infectious agents
Human oncogenic viruses:
 Contribute to 20% of all cancer (⅕)
 7 human viruses that cause cancer:
 DNA viruses:
- HHV8 (Kaposi’s sarcoma virus)- causes lymphoma
- HHV4 (Epstein Barr virus)- causes lymphoma
- Polyoma virus – causes Merkel cell lymphoma
- Hep B – causes hepatocellular carcinoma
 RNA Viruses:
- Hep C – causes hepatocellular carcinoma
- HTLV – causes Leukaemeia/ Lymphomas

Viral transformation of cells:
 Transformed cells are not infectious (non-productive, proliferative state)
 Virally transformed cells become immortalized (grow forever)
 Viral transformation is not a requirement (is accidental)
 Properties: altered morphology, lose contact inhibition, grow without attachment
to substrate, proliferate indefinitely, reduced requirement for mitogenic growth
factors, high saturation density, increased glucose transport.
 Viral transformation mechanisms:
- Carry modified cellular genes (v-onc) (RSV)
- Activate cellular protooncogenes (RSV)
- Express proteins that interfere with tumour suppressors (p53)
- Indirect methods, e.g. inducing chronic inflammation (HTLV-1, HBV and HCV)

Overview of the cell cycle:
Phases: G1, S, G2, M
Mitosis: prophase, metaphase, anaphase, telophase
Cyclins and CDKs control cell cycle
CKI’s (CDK inhibitors):
Cip/Kip family: Inhibit the ATP binding site of CDK
INK4 family: Inhibit the cyclin binding site
Regulation of CDK activity: Association with cyclin, activating and inhibitory phosphorylation,
CDK inhibitors
The restriction point:
pRb controls the G1/S restriction
Hypophosphorylated Rb binds to E2F and DP transcription factors
Hyperphosphorylated Rb releases E2F and DP: leads to cell proliferation

Transducing oncogenic retroviruses

(1) Rous sarcoma virus
 Experiment 1: 1911, Rous extracted a filterable agent that could transduce tumours
from one chicken to another chicken
- The viral oncogene was shown to be V-Src
- V-Src has a SH2, SH1 and SH3 domain

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