Tumor Viruses and Retroviruses

Question 1

Viruses that can cause cancer

Answer 1

Papillomaviruses

Hepadnavirus (Hepatitis B)

Flavivirus (Hepatitis C)

Herpes Virus (EBV)

Retroviruses (HTLV-1 and HIV)

Question 2

DNA viruses that contribute to cancer in humans

Answer 2

Herpesviruses - EBV. HHV-8
Papilloma viruses
HBV
Adenoviruses

Question 3

RNA tumor-causing viruses

Answer 3

Most RNA tumor-causing viruses are retroviruses.
Not all retroviruses are tumor-causing viruses

HTLV-1, HTLV-2 Both can cause Adult T cell leukemia (ATL)

HIV-1, HIV-2 Do not directly cause cancer but HIV-1 + HHV8 infection can lead to Kaposi’s sarcoma.

Human spumavirus (foamy virus) is not associated with cancer.

HCV - hepatitis C virus

Question 4

Is there any virus that can directly cause cancer?

Answer 4

No. Induction of cancer requires many steps and

viral infection is only part of the process. Other genetic changes are required. It’s more of an initiator event

Question 5

EBV and cancer

Answer 5

Causes Burkitt’s Lymphoma - a B cell cancer - through
Chromosome translocations that activate c-myc oncogene

This occurs as a result of hyperproliferation of B cells induced by the virus, resulting in chromosome instability.

Also causes Nasopharyngeal carcinoma and Hodgkin’s lymphoma (Hodgkin’s Disease) - Malignant B cells in lymph nodes, often with infiltration of other cells

Question 6

HHV-8 and cancer

Answer 6

Kaposi’s sarcoma
Virus has several genes that regulate cell growth, including one THAT DEGRADES Rb TUMOR SUPRESSOR GENE !!!

Causes cancer of epithelial cells in HIV+ individuals with AIDS.

Question 7

HBV and HCV

Answer 7

Hepatocellular carcinoma

HBV found integrated into chromosomes

HCV mechanism is poorly understood but may lead to chromosome instability

Question 8

Mechanism of cancer causing in EBV

Answer 8

promotes the proliferation of infected cells, and it immortalizes B cells in culture through the action of several viral genes which help cellular profileration

These genes include: Transcription factors

Mimics of cellular receptors which induce cell activation and proliferation pathways
- they are mitogenic.

Genes which inhibit apoptosis - often increasing Bcl-2 expression.

All which allow the opportunity for other genetic defect to arise and promote tumorigenesis

Question 9

Mechanism of cancer causing HPV

Answer 9

HPV Types 16 and 18 cause 70% of cervical cancer cases. Cervical cancer is the second most common cancer in women.

HPV cause degradation of the p53 and pRb tumor suppressor genes through the action of its E6 and E7 proteins. (Thus E6 and E7 are oncogenes)

Progresses in stages, with early pre-cancerous stage containing cells that grow abnormally called cervical dysplasia or cervical intraepithelial neoplasia (CIN), abnormal growth of squamous cells on the surface of the cervix.

HPV Types 6 and 11 cause 90% of genital warts cases

Question 10

Cellular Gene mechanism for causing cancer

Answer 10

Either

1) Overexpression or an activating mutation of these oncogenes can lead to cancer
2) Inhibition or loss of function mutation of the protector genes can lead to cancer (p53, p16, Rb1)

Question 11

Oncogene

Answer 11

gene that can cause cancer, or at least hyperproliferation leading to the development of cancer. They’re genes that are controlling cell cycle. So a lot of viruses are going to screw around with that system.

Question 12

HPV Vaccine Gardasil

Answer 12

Gardasil - Merck
3 doses, vaccinates against HPV 6, 11, 16, 18

Must be given before infection

Viral capsid protein L1 self-assembles into virus-like particles, these are created in the lab and used in the vaccine to elicit protective antibodies; a GAG protein, which is a capsid protein, and they make it through DNA recombinant technology, and synthesize it in probably bacteria or yeast or something like that. And when they concentrate it to the critical concentration, it self-assembles as if it were a virus, into something that structurally looks like a virus but it is non-infectious,

HAS BEEN EXPANDED TO INCLUDE PEOPLES AGE 27-45

Question 13

Cervarix

Answer 13

Protects against HPV 16 and 18 but doesn’t offer protection against the HPV strains that can cause genital warts (6 and 11).

Question 14

Statistics on Men with HPV?

Answer 14

1 in 9 Men Have Oral HPV

Question 15

Who gave us HPV?

Answer 15

the inference is that this is sexually transmitted from Neanderthals.

Question 16

Retroviruses

Answer 16

Enveloped, +ssRNA genome; two copies of +ssRNA per virion

Replicate through a dsDNA intermediate created by a viral RNA-dependent DNA polymerase called reverse transcriptase (RT).

This DNA copy is then integrated into the chromosomal DNA becomes part of the cell, stays with the cell for life.

Question 17

Examples of Human Retroviruses

Answer 17

HTLV-1 
HTLV-2  
HIV-1 
HIV-2
Human spumavirus (foamy virus)

Question 18

Retroviral replication cycle

Answer 18

1) The virus binds to the cell through fusion
2) delivers its RNA and undergoes reverse transcription into a DNA copy
3) DNA migrates to the nucleus
4) integrates into your DNA

5) Hijacks cellular replication machinery and is there for the life of the cell.

Note you are making RNA of the full length virus, and this is used to make new genomes that are packaged into virions, and to encode proteins that are made to assemble the virions. So this is doing double duty. And that’s true for any retrovirus

Question 19

Four methods of Retroviral Oncogenesis

Answer 19

1) Delivery of a viral oncogene (v-onc) into a cell by infection (no human equivalent but happens in chickens and mice)
2) Activation of a cellular oncogene (c-onc) by integration of retrovirus near it; the viral promoter drives improper expression of the cellular oncogene causing too much c-onc is made, or it is made in the wrong cells.
3) Inactivation of a tumor suppressor gene by integration of a retrovirus within it; this disrupts the gene.
4) Retroviral transcription factors

HTLV Tax protein is a transcription factor that stimulates replication of infected T cells
HIV Tat protein is a transcription factor that assists HHV-8-induced transformation.