DNA Oncogenic Viruses

Several DNA viruses are associated with, and are important in, the etiology of certain human cancers. For example, chronic infection with hepatitis B or C virus (HBV, HCV) is associated with liver cancer, infection with human papillomavirus (HPV) type 16 and type 18 is associated with cervical cancer, and infection with Epstein-Barr virus (EBV) is associated with Burkitt s lymphoma. About one-fifth of human cancer worldwide is associated with DNA oncogenic viruses. In 2006, the FDA approved a vaccine against HPV 16 and 18, which are responsible for about 70% of cervical cancer cases. 

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Many animal viruses, particularly the oncogenic viruses—either directly or, in the case of RNA viruses such as HIV that causes AIDS, their DNA transcripts generated by the action of the viral RNA-dependent... 

The presence of contamination with oncogenic virus DNA (depending on whether a bacterial or mammalian system was used on the synthesizing agent) or endotoxins ... 

Some viruses are known to cause cancer these include both DNA and RNA viruses, retroviruses. These oncogenic viruses possess oncogenes in their genome. 

Oncogenic viruses 248 One-start helix 334 Oparin, I. V. 9 Open systems 289 Operator sequence of DNA iH NMR spectrum 269 Operons 240 Opsin(s) 553 Optical rotation 42 Optimum rate for enzymes 469 d Orbitals, participation in covalent bond formation 311 Orcinol 251 Ordered binding 464 Ordered sequential mechanism 475 Organelle(s) 11... 

Levine, A. J., The p53 protein and its interaction with the oncogene products of the small DNA tumor viruses. Virology 177 419-426, 1990. 

In general, cells transfected with DNA that contains transforming genes, derived from oncogenic viruses, lose the growth feature called contact inhibition, which limits their growth and proliferation. These transfectants can be visualized under the microscope and isolated as colonies. 

The rDNA-derived products may contain potentially harmful contaminants that are normally not present in their equivalents prepared by chemical methods, and which the purification process must be capable of eliminating, such as the endotoxins expressed in bacterial cells, cellular DNA, and viruses of animal origin. Contamination with nucleic acid from transformed mammalian cells is of particular concern due to the possible presence of potentially oncogenic DNA. 

It is known that RNA oncogenic viruses require DNA synthesis for their replication. As distamycin/A blocks some early steps in the growth cycle of DNA viruses, probably connected with DNA replication32, it was of interest to investigate the effect of distamycin, distamycin-4 and distamycin-5 on MSV (Moloney). 

It has been recently reported34 that DNA polymerases of several oncogenic viruses are inhibited by ethidium bromide to different degrees according to the nature of the template used and the source of the enzyme. The effect of distamycin derivatives on the DNA polymerase activity of FL virions was therefore studied in the presence of poly (dA—dT), poly (dl dC) and poly (rA) (dT)g (Table 6). The DNA polymerase activity was found to be most sensitive to distamycin inhibition with poly (dA-dT) as primer-template and somewhat less so with poly (rA) (dT)g. In both cases the inhibitory response of the antibiotic increases according to the number of pyrrole rings in the molecule. With poly (dl - dC) as template no significant inhibition of DNA polymerase activity by distamycin derivatives was observed. 

The experiments reported here demonstrate that the distamycin inhibition of DNA polymerase activities of FLV and MSV-M are template specific. Templates containing thymine and adenine are highly sensitive to the action of distamycins. This inhibition is dependent on the number of pyrrole rings in the molecule. The inhibition of DNA polymerases of RNA oncogenic viruses and the foci formation by distamycin derivatives conclude that both activities are dependent on the same structural component(s) of the molecule. 

DNA viruses. Some DNA viruses also cause human cancer, but by different mechanisms. Three DNA tumor virus families, SV40, papillomavirus, and adenovirus, encode proteins that inactivate pRb and p53. By interfering with the Gl/S checkpoint, these oncoproteins increase the probability that mutations in oncogenes and tumor suppressor genes will be incorporated into the genome of infected cells, thereby increasing the probability of transformation. The Epstein-Barr virus encodes a Bcl-2 protein that restricts apoptosis of the infected cell. 

Ans. Retroviruses are RNA viruses that reproduce through the intermediate formation of DNA. The retrovirus contains genetic information for the synthesis of the enzyme reverse tramcriptase. Reverse transcriptase, synthesized using the host cell s mechanism for protein synthesis, directs the synthesis of viral DNA from viral RNA. Subsequently, the host reproduces the viral RNA using the DNA as a template. The retroviruses include HIV and cancer-causing viruses (oncogenic viruses). 

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