MIC 252 42. Interactions of Human Cancer Viruses with their Hosts

1. MIC 252 42. Interactions of Human Cancer Viruses with their Hosts • Learning Outcomes • Describe how tumour viruses can cause permanent malignant changes within cells • List and describe the various viruses and the cancers with which they are associated Learning outcome #2 important.

2. Viruses and Cancer • Variety of RNA and DNA viruses can cause permanent malignant changes in cells • These changes can be: • In morphology- loss of shape, rounding, decreased adhesion to surface • In growth or contact- loss of contact inhibition, immortalisation • In cellular properties- chromosomal changes, appearance of new antigens • In biochemical properties- loss of fibronectin, reduced cAMP Learning outcome #2 important.

3. Oncogenes • Changes come about after insertion of viral nucleic acid into host genome • These nucleic acids are usually genes (oncogenes) that interfere with growth-regulating factors • E.g., src gene from the Rous sarcoma virus interfere with tyrosine kinases • Normal human cells contain many oncogenes  as much as 0.3% of the mammalian genome • Some conserved because of a valuable function • Can be carried from one cell to another and one host to another • Small number of human cancers are associated with tumour viruses Learning outcome #2 important.

4. Human T cell Lymphotropic Virus (HTLV) • HTLV1 and HTLV2 are retroviruses with no oncogenes • Proviral DNA is detected in cellular DNA of certain malignant lymphomas and leukemias • Carcinogenic nature of HTLV1 is not due to the activation of cellular oncogenes but from tat gene product that enhances host DNA transcription involved in cell division • Confined mostly to Southern Japan, Caribbean islands and West Africa Learning outcome #2 important.

5. Epstein-Barr Virus (EBV) • Closely linked with the development of nasopharyngeal carcinoma • Common in Southern China, Asia and less common in North Africa • No convincing evidence for specific carcinogenic EBV strains  could be due to the presence of nitrosamines (carcinogen) in salted fish • EBV DNA can be demonstrated in cancer cells Learning outcome #2 important.

6. Epstein-Barr Virus (EBV) • Associated with Burkitt’s lymphoma- tumor of immature B cells • Parts of East Africa, Papua New Guinea in young children- especially boys • EBV DNA is present in tumor cells but most of the copies are not integrated into the host genome • EBV causes B cells to proliferate which activates cellular oncogenes like c-myc • B cells prevented from entering a resting stage  downregulation of adhesion and HLA molecules  B cell not under immune control Learning outcome #2 important.

7. Human Papilloma Virus (HPV) • Distinct association between development of cervical cancer and some of the HPV’s • They account for > 80% of cervical cancers • Also penile, vulval, rectal cancer • Types 16 and 18  high risk • HPV genomes integrated with host genome • Also associated with squamous cell carcinoma of the skin • UV light act as carcinogen Learning outcome #2 important.

8. Hepatitis B and C (HBV and HCV) • Major causes of hepatocellular carcinoma (HCC) • More common in West Africa due to carcinogens like aflatoxin • HCV causes cirrhosis that drives the formation of HCC • In addition- several DNA viruses can transform cells in which they cannot replicate Learning outcome #2 important.

9. Viruses and Human Cancer Learning outcome #2 important.