Oncogenic viruses Flashcards
1
Q
Overview of oncogenic viruses
A
- no characteristic shape. genome or mechanism
- no characteristic target cell, patient or pathway
- animal models are not reliable predictors of human effects
2
Q
Features of human cancer cells
A
- make tumors if transplanted to animals
- undifferentiated
- immortal
- not contact inhibited
- resistant to apoptosis
- abnormal chromosomes
3
Q
Genes that control the growth of human cells
A
- myc: transcription factor
- src: membrane signaling of growth factor binding
- ras: signal transduction from surface receptors
- sis: platelet-derived growth factor
- erb B: growth factor receptor
- fms: growth factor receptor
- LMO2: hematopoiesis
- they are called proto-oncogenes
4
Q
Cell cycle control
A
-inactivation of P53 or Rb allows cells to proliferate and accumulate other mutations
5
Q
Oncogenes are overexpressed in some human cancers
A
- acute myeloblastic leukemia: mos
- chronic myelogenous leukemia: abl
- acute promyelocytic leukemia: fes
- acute lymphocytic leukemia: LMO2
- ovarian cancer: myb
- breast cancer: her-2/neu
- by amplification, mutation or translocation
6
Q
P53 and cancer
A
- breast, bladder, prostate, liver, lung, skin, colon
- Rb may also be mutated (e.g. Retinoblastoma)
7
Q
Cell transformation and viruses
A
- RNA oncogenic viruses carry activated oncogenes, or insert their promoter and activate an oncogene
- DNA oncogenic viruses degrade cell cycle genes
8
Q
Oncogenic viruses are species specific
A
- 1955- inactivated polio vaccine introduced (Formalin treated)
- 1960- live attenuated polio vaccine introduced, each one prepared in monkey kidney cells
- by sept 1961- 60% of population vaccinated
- by 1967 cases of polio reduced from 76,000 to 1,013 now 5-10 cases per year in US
- 1960-found that monkey kidney cells cause sarcome in hamsters- a new virus (SV40) that transformed hamster and human cells, immunized children shed the virus for several weeks in stool, transformed human cells make tumors in animal recipients
9
Q
SV-40
A
- prototype DNA tumor virus
- T antigen allows cells to proliferate without control- T antigen has to be expressed continually for tumor to grow
10
Q
Species specific oncogenic adenoviruses
A
- human virus of specific serotypes
- cause cancer when injected to newborn rodents
- E1A and E1B are analogous to T antigen and are always expressed in transformed cells
- not responsible for any human cancers
11
Q
Example of non-species specificity
A
- gene therapy viruses can have side effects- 3
- SCID-X1- IL2 receptor deficiency in newborns
- mouse leukemia virus modified to transduce stem cells
- apparent cure of 1 case in England and 10 cases in France
- but 4/9 developed T cell leukemia due to insertion of virus adjacent to LMO2 oncogen
12
Q
Animal cancers caused by viruses
A
- virus- sarcoma viruses of cats, chickens and rodents= sarcoma
- mammary tumor virus of mice = breast cancer
- feline leukemia virus = leukemia
13
Q
Viruses that cause cancer in humans
A
- papillomaviruses- cervical cancer (also warts)
- Epstein Barr virus- Burkitts lymphoma (mono)
- Hep B virus- Hepatocellular carcinoma
- Kaposi’s sarcoma HHV8
- Human T cell leukemia virus - leukemias/lymphomas
14
Q
Human papillomaviruses
A
- related to Sv40 virus
- over 100 types
- low risk -4,6,8- warts
- intermediate- 11- laryngeal papillomas
- high risk - 16, 18- cervical, pharyngeal cancer
15
Q
Functions of HPV E6 and E7
A
- E6 binds P53- leads to degradation by ubiquitin pathway
- E7 binds non-phosphorylated Rb- prevents its interaction with E2F
- transfection of cells with E6/E7 leads to immortalization
- co transfection with mutated ras leads to transformation
- E6 and E7 of low risk HPVs are similar but low affinity binding
- E2 normally suppresses E6 and E7 loss of E2 function because of integration therefore allows over-expression of E6 and E7
