Virus and Cancer

Viruses are usually not complete carcinogens in human cancers Tumor viruses establish chronic infections in humans Cancer is an accidental side of viral replication strategy

Two classes of genes Oncogenes: These are stimulatory for growth, cause cancer when hyperactive. Tumor-suppressor genes: genes that inhibit cell growth and cause cancer when turned off.

How do Virus get involved? Virus can either carry a copy of one of these genes or can alter expression of the cell’s copy.

What is a virus? Non-living particle Consisting of proteins and nucleic acid, either DNA or RNA at its core A Virus

RNA Can not replicate on its own, uses host machinery to replicate. Entrance is gained through receptors on the cells. Once inside, viral RNA is reverse read to make a segment of DNA Reverse Transcriptase

Viral Replication 4 steps 1. Attachment and entrance 2. Synthesis of proteins 3. Assembly of new virus 4. Release of new virus particles (lytic or lysis) http://schoolworkhelper.net/viral-replication-lytic-cycle/

Virus to Cancer DNA Tumor viruses 2 life styles A permissive cell: all viral parts are replicated Lysis and death of cell A non-permissive cell: DNA integrated into the cell chromosome randomly. Only parts are expressed No progeny released.

How the virus works in two disorders Hepatitus C Cervical Cancer

P53 (tumor suppressor) P53 gene P53 gene P53 gene Hepatitis C Papilloma P53 P53 P53 A similar thing happens to p53 protein in hepatitis C-infected cells and p53 is bound so that it becomes inactive. Again, lack of p53 results in loss of growth control. In papilloma-infected cells, things happen a little differently. In this case the virus makes a protease that destroys p53 protein. Thus, our knowledge of how RNA tumor viruses cause tumors led to the discovery of viral oncogenes. This led to the discovery of cellular oncogenes which in turn led to anti-oncogenes. The discovery of anti-oncogenes showed how DNA tumor viruses cause tumors. Papilloma proteolysis P53 DNA Stops replication replication replication

Hepatitus C Viral proteins interact with p53 and lead to cell proliferation and prevents apoptosis Transfers by blood Liver damage, such as cirrhosis, or scarring of the liver Liver failure Need for a liver transplant Liver cancer Death

Human Papillomavirus Malignant carcinomas DNA Virus 8 kilobases long >100 types of HPV Cause warts – benign Malignant carcinomas epidermodysplasia verruciformis Autosomal recessive mutation leads to abnormal uncontrolled virus replication. Penile, uterine, cervical, canal carcinomas http://www.ansci.wisc.edu/jjp1/ansci_repro/misc/project_websites_07/tue07/HPV_Vaccine/What%20is%20HPV.html

HPV

Cervical Cancer New cases 2012 US: 12,170 Deaths: 4,220 average age at death 57 yrs Incidence rate: 8.1 per 100,000 women Hispanics 11.8 per 100,000 women Lifetime Risk for women born today- 1 in 147. All statistics from the National Cancer Institute, Surveillance Epidemiology and End Results. A small but significant proportion of human cancers are caused by mechanisms that involve viruses, bacteria or parasites (15%).

Symptoms

Diagnosis

Treatment Precancerous lesions Cryosurgery (freezing) Leep- loop electrosurgical excision procedure. Laser vaporization Cancerous tissue Surgery Radiation Chemotherapy Surgery is radical hysterectomy

New Treatment: Guardacil From the U of Rochester HPV Vaccine Protects against 4 types of HPV “2 types of HPV that cause about 75% of cervical cancer cases, and 2 more types that cause 90% of genital warts cases. In boys and young men ages 9 to 26, GARDASIL helps protect against 90% of genital warts cases” (Guardacil.com)

How a vaccine works

Cutting edge research Penn Medicine, University of Pennsylvania Immunotherapy program Personalizing approach that boosts the bodies own immune system to attach tumors. Using the patients own tumor proteins in a vaccine. Using the patients frozen turmor protein is extracted (lysate). This is injected into the patient every 2 weeks, 5 times total. A CT scan assess the tumor. http://www.uphs.upenn.edu/obgyn/research/ovarian_clinical.htm

Conclusion Virus can show up in the DNA of a host, damaging the cell cycle, causing uncontrolled growth of a cell. Virus that are carcinogenic are passed in body fluids. Be safe. Consider a vaccine to help prevent cervical cancer. Safe sex, don’t share needles,

References Hunt, R. 2009. Microbiology and Immunology on-line, University of South Carolina School of Medicine. http://pathmicro.med.sc.edu/lecture/retro.htm Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Altekruse SF, Kosary CL, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975- 2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD National cancer institute. National institute of health. http://www.cancer.gov/cancertopics/pdq/treatment/cervical/Patient/pa ge2 Ovarian Research. Penn Medicine, University of Pennsylvania. Available at http://www.uphs.upenn.edu/obgyn/research/ovarian_clinical.htm