CANCER CAUSING VIRUSES

 Can this really happen??  Think about this for a moment. Viruses causing cancer??  According to researchers, some of the more common viruses that occur today have the potential to cause certain cancers Cancer Cell VIRUSES CAUSING CANCER?

Specific VirusesCancers CausedMechanism that causes cancer Epstein-Barr Virus (EBV)Burkitt’s Lymphoma, Hodgkin’s Lymphoma Cell proliferation, inhibition of apoptosis, cell migration Hepatitis B Virus (HBV)Hepatocellular CarcinomaInflammation Hepatitis C Virus (HCV)Hepatocellular CarcinomaInflammation Human Immunodeficiency Virus (HIV) Kaposi's Sarcoma, Lymphoma Indirect action of immunosuppression Human Papilloma Virus (HPV) Cervical CancerInhibition of DNA damage response, anti-apoptotic activity Human T-cell Lymphotropic Virus Adult T-cell Leukemia and Lymphoma Immortalization and transformation of T-cells

 Researchers are not 100% sure of how a virus may cause tumor formation, but there are a few methods that are being proposed and studied SO HOW DO THESE VIRUSES CAUSE CANCER?

 The first theory is that a virus interrupts the natural cell cycle in some way. Dr. Yuri Lazebnik at Cold Spring Harbor Laboratory found that fusing normal cultured human cells and Mason-Phizer Monkey Virus (MPMV) did NOT cause the cells to proliferate (meaning grow) uncontrollably  Wait, if fusing a virus and a normal cell DID NOT cause uncontrollable growth, how can this cause cancer??  The same researchers found that if one of the original cell partners (human cell or monkey virus) carried a “pre- disposing” mutation then a large percentage of the resulting hybrid cells would grow uncontrollably and become potentially cancerous

 When the cells that had the pre-disposing cells were fused, mutations showed on the oncogenes (specifically E1A and Myc) or to the tumor suppressor gene, p53.  If oncogenes are activated, cancerous cells are encouraged to grow. If the tumor suppressor gene p53 is deactivated, the cells are not signaled to stop growing at any time and continue to grow uncontrollably

 Normally, when a virus inserts itself into a cells DNA structure, it is able to “hide” from the body’s immune system and it is not eliminated from the host  Later, these host cells are found to have proof of a previous infection. The virus left evidence of an infection-much like fingerprints at a crime scene HIT AND RUN THEORY

 Cells with certain mutations normally will self-destruct so that they do not turn cancerous, but the viruses interfere with this defense mechanism  The hit and run theory proposes that a virus can cause cancer without inserting itself into the host cell’s DNA

 A cell develops a genetic mutation, but the virus present in the cell overrides the defense mechanisms and allows the cell to continue to live. Over time, more and more mutations develop, and the cell turns cancerous  However, by the time the cancer is discovered, the virus has been eliminated by the immune system, leaving behind no “fingerprints”

 “Viruses don’t set out to cause cancer, but their replication uses all the same functions. So they tend to inhibit the whole set of these protective mechanisms,” Stevenson said, “so they are kind of ideal agents for causing cancer” “QUOTE OF THE DAY”

 Transformation of a cell can cause  Loss of growth control  An ability to form tumors-viral genes interfere with control of cell replication  Transformed cells frequently exhibit chromosomal abnormalities Viral Transformation The changes in the biological functions of a cell that result from Regulation Of the cells metabolism by viral genes and that confer on the infected cell certain properties characteristic of Neoplasia These changes often result from the integration of the viral genome into the host cell DNA Source:faculty.easnville.edu/md7/bact02/retro/retro_file/retro.ppt TUMOR VIRUSES

 DNA Tumor Viruses  Uses host mechanisms to create new viral particles  Examples: Papilloma viruses, Herpes Viruses, etc.  RNA Tumor Viruses  Carries its own RNA polymerase to create new viral particles  Examples: Human T-cell Lymphoma, Human Immunodeficiency Virus, etc. MAJOR CLASSES OF TUMOR VIRUSES

 Papilloma Viruses  Cause natural cancers in animals  Cause benign warts  Ubiquitous  Human Papilloma Virus (HPV)  Persistent HPV infections are now recognized as the cause of essentially all cervical cancers  It was estimated that in 2010, women would be diagnosed with cervical cancer with 4000 cases resulting in death  HPV types 16 and 18 transform certain gene products in the cell that bind to the cell cycle control agents, the Rb and p53  Note: p53 is the cells tumor suppressor gene…. DNA TUMOR VIRUSES

 Herpes Virus  Considerable evidence for role in human cancer  Some are very tumorigenic in animals  Viral DNA found in a small proportion of tumor cells “hit and run”  Some cancers possible caused by herpes viruses (specifically Epstein-Barr Virus)  Burkitts Lymphoma  Nasopharyngeal Cancer  This virus transforms human B-lymphocytes in vitro (possible mechanism) DNA TUMOR VIRUSES

 Hepatitis B Virus (HBV)  Can cause Hepatocellular Carcinoma  The cancer MAY be caused by the chronic inflammation of the liver  The mechanism that inflammation causes in the promotion of cancer is not well understood, but there is evidence of a hit and run mechanism  There have been no viral oncogenes found in HBV particles as of yet  There have been studies that suggest the deletion of the p53 gene may play a role in the proliferation of mutated liver cells  *note: Hepatitis C Virus (HCV) is believed to cause Hepatocellular carcinoma as well, though it is RNA Tumor Virus DNA TUMOR VIRUSES

 Some DNA viruses…  Can transform cells or have lytic life cycle  Often integrate into the host genome  In transformation only genes are transcribed DNA TUMOR VIRUSES IN HUMAN CANCER

 Retroviruses known to cause human cancer  Human T-cell Lymphotropic Virus  Causes Adult T-cell leukemia and hairy cell leukemia  Human Immunodeficiency Virus  Can lead to Kaposi’s Sarcoma How do retroviruses transform Animal Cells?? The genetic information that leads to cellular transformation has no role in the viral reproductive cycle and in some cases, is not even contained in the genome of the virus Some viruses contain another gene that is a tumor causing gene called an oncogene. These retroviruses are called transducing viruses. RNA TUMOR VIRUSES

 Oncogenesis is the result of genetic changes that alter the expression or function of proteins that play critical roles in the control of cell growth and division  Oncogenic viruses cause cancer by inducing changes that affect cell growth and division  Cancer arises from a combination of dominant gain of function mutation in proto-oncogenes and recessive loss of function mutations in tumor suppressor genes Watch: Oncogenes Source: ONCOGENIC VIRUSES

 Different types of cancers are named according to the type of tissue they inhabit.  -oma=a benign tumor of any tissue group  Carcinoma=cancer of the epithelial tissues (this does not just mean the outside layer of skin. This includes ALL epithelial layers of the body systems)  This layer of tissue arises from the ectodermal region of embryonic development  Sarcoma=connective tissues  This layer of tissue arises from the mesodermal region of embryonic development NAMING CANCERS

 Examples:  A benign fatty mass  =lipoma  A malignant tumor that involves glandular tissues  =adenocarcinoma  A malignant tumor that involves the bone  =osteosarcoma  Also, the term in situ means pre-invasive. Cancers that have not spread through their original basement membrane will have this designation  Ductal Carcinoma In Situ (DCIS) is a cancer of the milk ducts in a woman’s breast. The cancer is confined to the ductal region and is considered an early stage of breast cancer

 Wordpress.com  Sciencephoto.com  Cancer.gov  www,cancerhelp.org.uk    Faculty.clintoncc.suny.edu  Irapilgrim.mcn.org   Faculty.eansville.edu/md7/bact02/retro/retro_files/retro.ppt SPECIAL THANKS TO….