Viruses oncogene association with

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. 

Another useful aspect in oncology is the detection of tumor-assodated viruses, which are important for tumor diagnosis, therapy and dinical follow-up. Using specific primers and probes complementary to virus genomes, provide a powerful and sensitive method to detect many viral genes and oncogenes associated with different types of malignancies such as HPV, EBV, HHV-8 and HCV. 

The term oncogene was coined in association with the search for the tumor-causing principle in retroviruses. Retroviruses contain RNA as the genetic material and can transcribe RNA into DNA with the help of the virus s own enzyme reverse transcriptase. The DNA form of retroviruses can integrate into the DNA of the host cell and, during cell division, is passed on to the daughter cells as a provirus. From the provirus, viral RNA and complete virus particles may be formed. 

HIV-1 and other retroviruses. Because of their association with viral oncogenes (Chapter 11) and because of the human immunodeficiency virus... 

Oncogenes Are Frequently Associated with Tumor-Causing Viruses... 

The oncogene of the FBJ murine osteosarcoma virus (fos) codes for a related nuclear protein that participates in transcriptional regulation. In human fibroblasts the fos protein is mostly associated with c-jun. The fos-jun complex binds specifically to DNA. Since fos alone does not show specific DNA binding, it is believed that jun is responsible for this affinity. Although jun can form homodimers that bind to DNA, the heterodimers formed between fos and jun show a greater affinity. The heterodimers are also more effective in transcription activation therefore the heterodimer is probably the functionally relevant state of the jun and fos proteins. 

Finally, the expression of viral genes is a hallmark of certain tumors, such as Burkitt s lymphoma. To direct gene expression selectively to Burkitt s lymphoma cells, regulatory elements responsive to the Epstein-Barr virus-(EBV-) encoded transcriptional activators, EBNA-1 or EBNA-2, have been used to construct promoters with an extremely high degree of specificity [76-78], Obviously, this kind of approach might be applicable to a variety of human tumors that have been associated with specific oncogenic viruses. 

Src is a oncogene first found in the Rous sarcoma virus where it encodes the pp60 kinase. The corresponding cellular kinase is pp60 -s =. The Src kinases are regulated by phosphorylation de-phosphorylation. Members of the Src family of cytosolic tyrosine kinases with important funtions in cell signalling are for example Yes, Fyn, Lck, Blk, Btk, Csk, Hck, Fgr and Yrk. Fyn associates with the p85 subunit of 1-phosphatidyl inositol... 

The c-myc gene is the proto-oncogene of avian myelocytoma virus. It binds to DNA and is involved in transcription regulation. The gene product, p62, is located in the nucleus of transformed cells, and levels of c-myc correlate with the rate of cell division. The c-myc protein is essential for DNA replication and enhances mRNA transcription. Activation of the c-myc gene is associated with B- and T-ceH lymphoma, sarcomas, and endotheliomas. In leukemias and lymphomas, increased c-myc expression may be due to amplification or chromosomal translocation of the gene. In acute T-celi leukemias, there is an (8 14) (q24 qll) translocation that... 

Many tumor viruses have a particularly valuable property. They elicit cancerous changes in cells in an artificial culture medium. This transformation makes it possible to examine thoroughly interactions under controlled conditions, avoiding difficulties associated with experiments on animals, though some viruses are powerful oncogenic agents in animals and do not transform culture cells. The process of transformation includes important morphologic and biochemical... 

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