RNA Tumor Viruses

Question 1

Intro

Answer 1

Only Oncovirus subfamily of the retroviruses have oncogenic potential for certain permissive cells
Viruses cause transformation by:
– introduction of oncogenes
– insertional activation or promoter insertion
– transcriptional activation

Question 2

Retroviridae

Answer 2

Contain a helical nucleoprotein complex inside an icosahedral capsid which is enveloped
Undergoes reverse transcription
Genome (as DNA) integrated into host DNA
Cause tumors
Some members carry oncogenes
HIV-1, the cause of AIDS

Question 3

Retroviruses, Ctd.

Answer 3

Sub families:
Lentiviruses
HIV – man
Visna – sheep

Spuma viruses
Foamyvirus

Onco viruses – ONLY ONES THAT TRANSFORM CELLS
Types B, C, and D

Question 4

Retroviruses, ctd.

Answer 4

Oncoviruses:

Morphological types

Type A - immature, intracytoplasmic

Type B - mature, e.g., mouse,
mammary tumor virus

c) Type C - mature, e.g., HTLV-1

Question 5

Retroviruses Ctd

Answer 5

Exogenous type C viruses

Spread horizontally; behave as infectious agents
When oncogenic, mainly cause tumors of reticuloendothelial system and hematopoietic systems (leukemia, lymphomas) or connective tissue (sarcomas)

Found in all cells of all individuals of a species
Viral information – is a constant part of genetic constitution; not pathogenic for host; can be activated by radiation, chemical carcinogens or metabolic inhibitors

Question 6

Retroviruse Replication

Answer 6

The viral genes involved in replication are called virogenes, e.g., gag, pol and env
Replication involves reverse transcription and the integration of the DNA into host cell DNA
A cartoon animation of the replication process is found at: http://www.mcb.uct.ac.za/tutorial/calgary_files/ under positive sense RNA viruses and retroviruses

Double strnaded DNA made in cytosol from reverse transcriptase. Strand enters nucleus and is partially encoded into host cell chromosome by integrase. Transcription makes mRNA & positive-sense RNA used in translation to make proteins. …again, HIV drug targets protease that cuts long polypeptide.

Question 7

Replication Patterns of Oncoviruses, cont.

Answer 7

If viral DNA is incorporated next to oncogene, mistake in oncogene can be made. This then goes into a virus. Virus enters another cell and makes product of viral gene and oncogene. CALLED VIRAL ONCOGENES (v-onc):

Viral copies of cellular oncogenes involved in cellular division or differentiation pathways
Include v-ras, v-sis, v-src, v-myc, etc

Sometimes viral genes get left behind and replication can’t occur in subsequent cells.

Infectious progeny virus formed
Include most leukemia viruses and Rous sarcoma virus, an acute tumor virus which contains virogenes and an oncogene

Question 8

Replication Patterns of Oncoviruses, cont.

Answer 8

C. Defective viruses (Figure 1)

Have lost part or an entire virogene which has been replaced by an oncogene
Require a helper virus for replication
Are acute transforming viruses

Question 9

examples of defective acute transforming viruses.

In all cases, they are acute becasue they introduce oncogenes that are not downregulated; they are gene product

Answer 9

Question 10

Mechanisms of Oncogenicity

Answer 10

A. Introduction of Oncogenes:
*Mechanism of transformation by acute transforming viruses utilized by both nondefective viruses (e.g., Rous sarcoma virus) and defective viruses (e.g., many sarcoma and acute leukemia viruses, like Abelson murine leukemia virus) to transform cells

Question 11

Mechanisms of Oncogenicity, cont.

Answer 11

B. Insertional activation or promoter insertion (e.g., chronic leukemia viruses and mouse mammary tumor virus):
*Involves viral promoters and transcriptional enhancer in LTR’s in activation of cellular oncogenes
*A mechanism of transformation by chronic transforming viruses
Diagrams of this mechanism may be viewed on Figures 19 and 20 at: http://pathmicro.med.sc.edu/lecture/RETRO.htm

Mechanism in which chronic leukemia viruses transmit themselves. Looking at genetic info, don’t see any oncogenes… Insertion next to genes that are usually downregulated. virus wants to make it’s copies and turns on the normally downregulated gene.

Question 12

Mech’s of Oncogenicity, ctd.

Answer 12

C. Transcriptional activation (e.g., HTLV-1 and 2):
*Involves transactivator proteins to activate cellular oncogenes
*The tax protein of HTLV-1 enhances transcription of viral genes and cellular genes like IL-2, IL-3, GMCSF and IL-2 receptor

These are the proteins that are needed to make mRNA of virus RNA/DNA, but ALSO ACTIVATES TRANSCRIPTION OF CELLULAR GENES (LIKE ABOVE) THAT ARE ACTIVATED IN CELLS READY TO DIVIDE