Micro: Oncogenic Viruses Flashcards
What is the frequency of virus-caused cancer?
15-20%
What are the epidemiologic criteria that define a tumor virus?
coincident geographic distribution of infection and cancer, higher rates of viral markers in the cancer, viral markers precede cancer, reduction of viral infections reduces cancer rates
What are the virologic criteria that define a tumor virus?
virus transforms cells in vitro, virus genome present in tumor but not normal cells, tumor induction seen in experimental animals
What are the 6 human cancer viruses, and what cancers do each cause?
- HTLV-1 –> ATL
- HHV8/KSHV –> Kaposi sarcoma, PEL, and Castleman’s
- EBV –> Burkitt’s Lymphoma, Hodgkin’s Lymphoma, posttransplantation lymphoma, Nasopharyngeal Carcinoma
- HPV –> cervical, penile, oropharyngeal carcinoma
- HBV –> hepatocellular carcinoma
- HCV –> hepatocellular carcinoma
What’s the difference between v-oncogenes and c-oncogenes?
v-oncogenes are derived from c-oncogenes that made their way into the viral genome in ancestors during normal replication cycle of retroviruses; now they are constitutively active viral genes that can cause cancer in a cell
Describe and distinguish transducing, nontransducing, and long latency retroviruses.
transducing = viruses that contain v-oncogenes and induce rapid and 100% tumor formation
nontransducing = contain no v-oncogenes but can activate c-oncogenes via integration
long lantency = has v-oncogene unrelated to c-oncogene; takes months to years to form tumor and does so at a low rate (<5%)
What are the 3 main mechanisms by which viruses cause cancer?
- activation of signaling pathways
- alteration of cell cycle regulation
- indirectly induce cell proliferation (ie., via tissue injury)
Describe the MOA of EBV and the cancer(s) it can cause.
EBV immortalizes B cells:
1. encodes LMP-1 – a constitutively active membrane signaling protein that activates kinase cascade, localizes NF-kappaB to the nucleus; increased transcription and cell immortalization
2. translocates c-MYC – placed downstream from active Ig heavy chain promoter, c-MYC is overexpressed, B cells are immortalized
Causes:
Burkitt’s lymphoma, Hodgkin’s lymphoma, posttransplantation lymphoma, and nasopharyngeal carcinoma
Describe the MOA of HHV8/KSHV and the cancer(s) it can cause.
encodes several cytokine homologues that stimulate transformation, most significant is vGPCR - constitutively active GPCR that induces growth
Causes:
-Kaposi’s sarcoma (lymphatic endothelial cancer)
-Pleural effusion lymphoma (non-Hodgkin’s body cavity lymphoma)
-Castleman’s disease (lymph node tumors, not strictly a cancer)
Describe the MOA of HTLV-1 and the cancer(s) it can cause.
infects and immortalizes CD4+ T cells:
expresses oncogene Tax which causes degradation of IkappaB, allowing NF-kappaB to immortalize T cells
Causes: adult T cell leukemia and lymphoma (ATL), which is a fatal aggressive non-Hodgkin’s lymphoma
Describe the MOA of SV-40 and the cancer(s) it can cause.
produces 2 version of “transforming” (T) antigens:
- small T binds phosphatase which extends the half-life of the phosphorylated protein
- large T binds RB and inactivates it, freeing E2F to the nucleus, and also binds p53, inactivating it
Causes: uncontrolled cell proliferation
Describe the MOA of HPV and the cancer(s) it can cause.
encodes E proteins needed for replication; in high risk strains these proteins bind and inactivate TSGs:
- E6 inhibits p53–>degradation
- E7 inhibits RB–>inactivation
Causes:
low risk strain (6, 11) cause warts
high risk strains (16, 18, 35) cause cervical, penile, oral/throat cancers
Describe the MOA of HBV/HCV and the cancer(s) it can cause.
these viruses cause chronic hepatitis, and the constant clearance of infected hepatocytes leads to unintended replication of hepatocytes, collecting subsequent mutations that lead to uncontrolled proliferation and cancer
Note: HBV produces protein X, a liver-specific transcription factor that may play a role in dysregulation of hepatocellular division
