Web & Social Media Analytics Previous Year Question Paper.pdf
Dibakar ppt
1. Tumor Viruses and Cell Transformation- Role in Cancer Initiation and Prevention
2. Tumor Viruses Lytic Life Cycle For most viruses: Genome viral proteins Replication Lysis Progeny virions
3. Tumor Viruses Latent Life Cycle Virus Cell Integration (usually) Transformation Virus-specific proteins expressed - No mature virus Changes in the properties of host cell - TRANSFORMATION
4. Tumor Viruses Transformation: Loss of growth control Ability to form tumors - viral genes interfere with control of cell replication
5. TRANSFORMATION Both DNA and RNA tumor viruses can transform cells Integration occurs (usually) Similar mechanisms VIRAL TRANSFORMATION The changes in the biological functions of a cell that result from REGULATION of the cell’s metabolism by viral genes and that confer on the infected cell certain properties characteristic of NEOPLASIA These changes often result from the integration of the viral genome into the host cell DNA
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7. Two Major Classes of Tumor Viruses DNA Tumor Viruses DNA viral genome Host RNA polymerase Viral mRNA Viral protein DNA-dependent DNA polymerase (Host or viral)
8. Important: Use HOST RNA polymerase to make its genome An enzyme that normally makes mRNA IMPORTANT RNA Tumor Viruses Viral RNA genome Reverse transcriptase (Virus-encoded) Viral DNA genome (integrated) DNA-dependent RNA polymerase ( Host RNA pol II) Viral genomic RNA Splicing (Host splicing enzymes) messenger RNA viral protein Virus
9. DNA Tumor Viruses DNA genome mRNA protein virus Host RNA polymerase II Host enzymes OR TRANSFORMATION In transformation usually only EARLY functions are expressed
10. DNA Tumor Viruses In Human Cancer Epidermodysplasia verruciformis Papilloma virus
11. DNA Tumor Viruses In Human Cancer ONCOGENE A gene that codes for a protein that potentially can transform a normal cell into a malignant cell An oncogene may be transmitted by a virus in which case it is known as a VIRAL ONCOGENE v-onc
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13. DNA Tumor Viruses In Human Cancer Host enzyme Viral enzyme Hepatitis B Virus DNA genome RNA polymerase II RNA Provirus Reverse transcriptase DNA genome
14. DNA Tumor Viruses In Human Cancer Hepatitis B continued Epidemiology: Strong correlation between HBV and hepatocellular carcinoma China: 500,000 - 1 million new cases of hepatocellular carcinoma per year Taiwan: Relative risk of getting HCC is 217 x risk of non-carriers
15. RNA Tumor Viruses RNA Genome - Retroviruses RNA-dependent DNA Polymerase encoded by virus REVERSE TRANSCRIPTASE RNA genome Reverse transcriptase DNA genome Integrase Integrates Host RNA polymerase II RNA genome host virus virus
22. RNA Tumor Viruses Retrovirus Life Cycle Endocytosis Fusion of membranes Release of nucleocapsid to cytoplasm Nucleus
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24. RNA Tumor Viruses Drawback to this lifestyle Genomic RNA DNA Genomic RNA Pol II is a host enzyme that, in the uninfected cell, makes mRNA When making mRNA, pol II does not copy entire gene to RNA Host RNA pol II Reverse transcriptase
25. primer Viral genomicRNA Reverse transcriptase dsDNA Result: New copy of viral RNA is shorter - lacks control sequences Problem of using RNA pol II to copy a gene RT promotor RNA synthesis initiation site RNA pol II RNA synthesis termination site
26. RNA Tumor Viruses Clue: Difference in the two forms RNA R U5 GAG POL ENV U3 R LTR Repeat region Repeat region DNA U3 R U5 GAG POL ENV U3 R U5
27. Feline Sarcoma Virus (FSV) R U5 dGAG FMS dENV U3 R Avian Myelocytoma Virus (MC29) R U5 dGAG MYC dENV U3 R Avian Myeloblastosis Virus R U5 GAG POL MYB U3 R Some retroviruses have an oncogene instead of their regular genes
30. RNA Tumor Viruses The discovery of the acutely transforming retroviruses that contain v-oncs explains how cancers may arise as a result of infection These viruses cause rapid cancer in animals in the laboratory
31. RNA Tumor Viruses In contrast: Chronically transforming retroviruses cause tumors inefficiently after prolonged period of time No oncogene! – How does it cause a tumor? R U5 GAG POL ENV U3 R Avian Leukosis Virus (causes lymphomas)
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33. Cancers often result from gene translocations Burkitt’s Lymphoma 8:14 translocation Break in chromosome 14 at q32 Acute myelocytic leukemia myc
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Notes de l'éditeur
In previous lectures we have looked at the replication of viruses. How the genome gives rise to viral proteins
Some viruses may lay latent in the cell for a very long time (and then may possibly lyse the cell). In this case only early functions of these viruses may be expressed. This results in virus proteins being expressed but no mature virus particles. The expression of these early virus proteins may nevertheless alter the properties of the infected cell. THE CELL IS SAID TO BE VIRALLY TRANSFORMED.
Viral genes interfere with cell replication control mechanism. NOTE: The early functions of DNA viruses do not make structural proteins but control cellular and viral genome replication.
Permissive cells: Replication, lysis and death Non-permissive cells: transformation. Usually DNA is integrated. Early functions only are expressed. Control information, rather than structural proteins
Most people have antibodies against EBV Why some populations get mononucleosis while others get tumors in not known Causes lymphoma in marmosets
Reverse transcriptase is not a capacity possessed by normal eucaryotic cells Many features are unique to retroviruses Very unusual mode of replication which gives them the potential to transform the cell But when it comes to how these viruses cause neoplasia, they may be very similar to DNA viruses Rous sarcoma virus in chickens was the first retrovirus to be discovered. It causes an aggressive acute cancer in chickens
Even though the virus RNA is same sense (positive) as mRNA, it cannot be translated directly as it is encapsulated by proteins. Thus it must be copied via a negative sense nucleic cid (in this case via DNA). Virus contains about 10 copies of reverse transcriptase. NOTE: Both copied of single strand RNA are identical
When integrated viral genes may or may not be expressed If expressed, all are expressed at least in the simpler retroviruses (why we shall see later) Whether host polymerase makes mRNA or genomic RNA depends on the processing by the host cell splicing enzymes Nucleocapsid assembly is in the cytoplasm and reverse transcriptase is packed into the virus Virus buds through the plasma membrane where it picks up the viral glycoprotein Maturation occurs in the budded virus
To make an RNA using RNA pol II, sequences other than those to be transcribed are required. Thus the DNA “gene” is bigger than the mRNA that is transcribed from it. These extra sequences can be upstream or downstream from the transcribed portion. They include: promotors, enhancers, termination sequences. Thus these “control” sequences will be lost on reconversion of the viral genome to RNA. These sequences are necessary for transcription of mRNA but not the translation of mRNA
These viruses cannot make all of their proteins and so need a co-infecting “helper” virus Viral oncogenes have three letter names e.g. src, myb
Retroviruses that cause acute transformation (rapid onset of neoplasia) such as RSV have an extra gene. These neoplasms are usually only seen in laboratory situations. The viral oncogene causes cells to be released from their normal growth controls. These extensively characterized genes are NOT UNIQUE to retroviruses. cDNA probes against viral oncogenes show similar homologues in NORMAL eucaryotic cells . These cellular homologues are not identical to the viral oncogene and it seems that the virus has picked up a cellular gene during its evolution. The discovery of normal homologues of viral oncogenes was a great step forward in the cell biology of cancer. The cellular proto-oncogenes are a family of genes that may underlie much of carcinogenesis. BUT a cellular oncogene does not cause cancer normally. Why does it do so in a virus?
Remember: A virus has only one end: to reproduce. This means that the genome and proteins have to be made in large numbers. So many more copies of the v-onc mRNA are made than the c-onc RNA. This over expression may be the basis of the transformation that is seen
Could the break and exchange of parts of chromosomes bring the c-onc under the control of a very active cell promotor? In Burkitt’s lymphoma there is a 8:14 translocation. Myc is at the break site on chromosome 8. What does it come next to on chromosome 14?
