Micro: Oncogenic Viruses Flashcards Preview

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Flashcards in Micro: Oncogenic Viruses Deck (13)
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1
Q

What is the frequency of virus-caused cancer?

A

15-20%

2
Q

What are the epidemiologic criteria that define a tumor virus?

A

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

3
Q

What are the virologic criteria that define a tumor virus?

A

virus transforms cells in vitro, virus genome present in tumor but not normal cells, tumor induction seen in experimental animals

4
Q

What are the 6 human cancer viruses, and what cancers do each cause?

A
  1. HTLV-1 –> ATL
  2. HHV8/KSHV –> Kaposi sarcoma, PEL, and Castleman’s
  3. EBV –> Burkitt’s Lymphoma, Hodgkin’s Lymphoma, posttransplantation lymphoma, Nasopharyngeal Carcinoma
  4. HPV –> cervical, penile, oropharyngeal carcinoma
  5. HBV –> hepatocellular carcinoma
  6. HCV –> hepatocellular carcinoma
5
Q

What’s the difference between v-oncogenes and c-oncogenes?

A

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

6
Q

Describe and distinguish transducing, nontransducing, and long latency retroviruses.

A

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%)

7
Q

What are the 3 main mechanisms by which viruses cause cancer?

A
  1. activation of signaling pathways
  2. alteration of cell cycle regulation
  3. indirectly induce cell proliferation (ie., via tissue injury)
8
Q

Describe the MOA of EBV and the cancer(s) it can cause.

A

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

9
Q

Describe the MOA of HHV8/KSHV and the cancer(s) it can cause.

A

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)

10
Q

Describe the MOA of HTLV-1 and the cancer(s) it can cause.

A

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

11
Q

Describe the MOA of SV-40 and the cancer(s) it can cause.

A

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

12
Q

Describe the MOA of HPV and the cancer(s) it can cause.

A

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

13
Q

Describe the MOA of HBV/HCV and the cancer(s) it can cause.

A

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