Lecture 4b: Mechanisms of Oncogenic Viruses

Question 1

Anchorage-independent growth

Answer 1

The ability of cells to proliferate while held in suspension.

Question 2

Nude strain mice

Answer 2

Mice lacking a thymus and are incredibly immunocompromised and are therefore highly receptive to engradted cells

Question 3

Two direct mechanisms for viral oncogenes

Answer 3

1. Viral oncogenes
2. Insertional mutagenesis

Question 4

Viral oncogenes

Answer 4

Viruses that carry an oncogene termed the “Viral oncogene” that overstimulates the normal host pathways that promote abnormal cell proliferation.

Question 5

Insertional mutagenesis

Answer 5

Viral trans-activating genes activate the expression of proto-oncogenes or inactivate tumor suppressor genes

Question 6

Indirect mechanisms of viral-induced oncogenesis.

Answer 6

Modulation of host immune responses by oncogenic viruses.
-Cause chronic inflammation that can lead to oncogenic transformation
-Reduce immune activity

Question 7

Origin of viral oncogenes

Answer 7

Retroviruses can acquire and transduce cellular genes

Question 7

Origin of viral SRC oncogene

Answer 7

ALV lacks viral oncogene and will “Kidnap” it via transduction of c-src gene. Cellular transformation results in excessive phosphorylation of cellular proteins by pp60v-src and the deletion of v-src abolishes the tumorigenic potential of SRV. The product c-SRC is over expressed and highly active

Question 8

Difference between human c-SRC, chicken c-SRC. and chicken v-SRC.

Answer 8

-Chicken v-Src lacks carboxy-terminal negative regulatory domain and contains 12 carboxy-substituted amino acids and numerous point mutations which cause high activity in this protein.

Question 9

Functions of Src C-terminal domain

Answer 9

Negative regulatory and tyrosine inhibitory function

Question 10

Two viral oncoproteins that mediate the induction of neoplasia by HPV.

Answer 10

E6 and E7

Question 11

Continued expression of high-risk HPV E6 and E7

Answer 11

Causes inactivation of the retinoblastoma pRB and p53 tumor suppressor pathways.

Question 12

Viral factor HBx

Answer 12

Key regulatory factor of the hepatitis B virus and the main etiology for HBV associated liver diseases such as cirrhosis and hepatocellular carcinoma (HCC)

Question 13

Consequences of chronic HBV and HCV infections

Answer 13

Stimulates an immune response that kills hepatocytes followed by liver regeneration. If the infection isn’t cleared the damage and regeneration cycles occur repeatedly which promotes accumulation of oncogenic mutations and epigenetic changes that lead to tumorigenesis.

Question 14

Expression of human T-cell leukemia virus type 1 (Tax oncoprotein)

Answer 14

Induces DNA damage as reflected in a significant increase of micronuclei in cells.

Question 15

Molecular mechanisms of viral oncogenes by insertional mutagenesis

Answer 15

Phenomenon where an exogenous DNA sequence integrates within the genome of a host organism. Retroviruses slowly activate proto-oncogenes by inserting their genome adjacent to these cellular genes or inhibiting tumor suppressor genes.

Question 16

7 known oncogenic viruses

Answer 16

1. Epstein-Barr syndrome
2. Hepatitis B virus
3. Human T-lymphotropic virus 1
4. Human papillomaviruses
5. Hepatitis C virus
6. Kaposi sarcoma associated herpesvirus
7. Merkel cell polyomavirus

Question 17

Human Endogenous Retroviruses (HERVs)

Answer 17

Retorviral sequences integrated into the genome during evolution and can be activated abnormally expressed in autoimmune, neurodegenerative, chronic inflammatory diseases, and cancer.