Oncoviruses Flashcards
T or F: 15-20% of all viruses can be attibuted to viral infection.
True.
How long does it take humans to show signs of cancer after getting infected with a virus?
- who is most suceptible?
- Takes YEARS
- Immunocompromised people are most susceptible to these viruses
T or F: for oncoviruses viruses depend on cancer is a step required for replication
False, viruses do not need to cause cancer to persist as a virus (no selective advantage?)
What 3 mechanisms do viruses use to cause cancer?
- Activate Signaling Pathways to Stimulate Constitutive Growth
- Release Cell Cycle control - allows for uncontrolled growth
- Infected cell destruction/clearance leads to unplanned regeneration
Why is it hard to prove that a virus caused a cancer?
Its difficult to prove that your virus wasn’t:
- a Virus that just took residence in a tumor
- just be a contaminant
How do you determine if a virus is oncogenic or not?
- Virus should transform cells in vitro
- Virus genome should be present in tumor but not in normal cells
- Tumor is induced in experimental animals
What 6 human viruses do we know to be oncogenic?
- Epstein Barr Virus
- Human Herpes Virus - 8 (KSHV)
- Human Papilloma virus
- Human T-lymphotropic virus type 1 (HTLV-1)
- Hepatitis B
- Hepatitis C
What is the only retrovirus known to cause cancer?
Human T-Lymphotropic Virus type 1
What is the difference between an immortalized cell line and a transformed cell line?
Immortalized - RETAIN original cell properties but grow indefinitely
Transformed Cells - Grow Indefinitely but LOSE many growth properties
What growth properties are often lost from transformed cells?
- Reduced Need for Serum Growth Factors
- Loss of Contact Inhibition
- Anchorage Independent (don’t have to adhere to anything- they just grow in SOFT AGAR)
- Appear Round as opposed to Typical Morphology
- May cause tumors when introduced into a suitable Animal
What does it mean to say that ALV (avian leukosis virus) and RSV (Rous Sarcoma virus) are transducing retroviruses?
- How often are tumors caused?
- Genome?
- Tumors caused 100% of the time
- V-oncogenes in their genomes that are always active
What is the difference between a transducing Retrovirus and a non-transducing retrovirus?
- speed?
Transducing - causes cancer 100% of the time because it carries the ONCOGENE with it.
- this happens quickly
Non-Transducing - causes transformation often times and there is still a High rate of transformation BUT the oncogenic gene IS NOT carried with the virus Instead the virus inserts close to a host oncogene causing its upregulation
- this take week to months usually
Differentiate Non-Transducing and Non-transducing long latency retroviruses?
- What is an example of the latter?
Nontransducing Retrovirus
- Doesn’t carry oncogene with it but inserts close to one
Nontransducing, Long Latency Retrovirus
- Doesn’t replicate quickly so tumor formation happens slowly over time (this can take years)
HTLV-1 is a Nontransducing Long Latency Retrovirus
What are v-oncs?
Constitutively activated components of a signaling pathway in the host
What disease is caused by HTLV-1?
- what oncogenes are involved?
- How does this work?
- Virus Type?
Adult T cell Leukemia and Lymphoma (ATL)
- aka infects and transforms CD4+ T cells
How:
- TAX (coded for by the virus) constituatively activates IKK which phosphorlyates IkB sending if for Ubiquitination at the 26S proteosome
- This leaves NFkB free do enter the nucleus and promote constant T cell proliferation
Type:
Nontransducing Long Latency Retrovirus
What diseases are caused by EBV?
- why does it cause these types of cancers?
Virus Lays Latent in B-cell and Epithelial cells - this corresponds to the type of cancer it causes in people.
- Burkitt’s Lymphoma
- Hodgkin’s Lymphoma
- Post-transcriptional Lymphoma
- Nasopharyngeal Carcinoma
What Makes EBV oncogenic?
- Encodes Latency Membrane Protein-1 (LMP-1) - a membrane protein that keeps the NFkB pathway on
- Leads to B cell immoraliztion through the same IKK and NFkB pathways that HTLV-1 does
What cancers/tumors are caused by KSHV (aka HHV-8)?
- where does this virus take up residence?
- Latent in B-cells mostly, but also monocytes, T cells, and endothelial Cells
Cancers:
- Kaposi’s Sarcoma (lymphatic endothelial cancer)
- Pleural Effusion Lymphoma (non-Hodgkin’s body cavity lymphoma)
Benign:
- Castleman’s Disease (lymph node tumors)
What are the underlying mechanisms to the oncogenicity of KSHV (HHV-8)?
- encodes Constitutively active GPCR = vGPCR, also encodes cytokines, chemokines, and apoptotic inhibitors that are thought to have less of an effect most imp.
- Encodes v-cyclin that binds and activates CDK6
- v-cyclin/CDK6 pathway cannot be inhibited by Cip or INK4
- Cell cycle stays activated
- No signal needs to be sent to the molecule for it to turn the disease on
How does Simian Virus 40 (SV40) lead to cancer?
- genome structure?
Genome:
- Polyoma Virus so genome is Circular RNA
Cancer:
- sT (small transforming protein) binds and INHIBITS protein phosphatase 2A (ser/thr phosphatase)
- This means signals take a longer time to get turned off and cell division gets disregulated
T or F: Replication proteins of DNA tumor viruses can also disrupt the cell cycle during non-lytic replication
True, HPV does this
What allows HPV to cause cancer?
normally HPV enters “Permissive” cells and replicates
sometimes HPV enters “non-permissive” cell
- when this happens virus can either (1) stay in the episome
(2) enter the host (human) chromosome - IF entry gets messed up E2 (regulatory gene) gets messed up and E7 and E6 get expressed always
- E7 binds Rb and E6 bins p53 leading to cell proliferation
What virus binds to Rb and p53 the same way that HPV does?
- SV40
By what mechanism do Hepatitis B and C lead to liver cancer?
- Unplanned Regeneration
**This is the Leading Cause of Liver cancer
What is the mechanism underlying how HBV and HCV cause cancer?
- Chronic Inflammation causes the liver cells that don’t really want to replicate to constantly regenerate
- Since they aren’t made for this many mutations accumulate over many years
***NOTE: NO ONCOGENES are needed (although some think a HBV X antigen may contribute the cancer)
Differentiate Unplanned Regeneration to Unplanned Longevity?
Unplanned Longevity:
- EBV can lead to Burkitt’s Lymphoma via t(8,14) with the H chain promoter region ending up beside c-MYC (oncogene)
- This translocation is because EBV causes B cells to liver longer than they were supposed to
Unplanned Regeneration:
- Is the opposite the Liver cells with HBV liver less time than their supposed to and increased turnover leads to mutation
T or F: almost all c-oncs have cellular origins
True - they are derived from some host’s onco-genes
OF THE 6 KNOWN tumor VIRUSES they account for 1/5 of HUMAN CANCERS
OF THE 6 KNOWN tumor VIRUSES they account for 1/5 of HUMAN CANCERS
Viruses use cellular pathways identified in non-viral cancers to cause transformation in cell culture and tumors in animals
Viruses use cellular pathways identified in non-viral cancers to cause transformation in cell culture and tumors in animals
