ADVANCED VIROLOGY CANCER VIROLOGY 4.pptx

Virology

1. ADVANCED VIROLOGY Prepared By Dr. Usman Aliyu Dutsinma Department of Microbiology

2. 2 TUMOR VIRUSES

3. VIRUSES ASSOCIATED WITH CANCER When a cell deviate from normal regulatory mechanisms and divides in an uncontrolled, unlimited manner forming an abnormal mass of tissues, it is called Neoplasms or tumors . When a tumor (neoplasm) do not invade surrounding tissue, it is called Benign. It rather displaces the adjacent cells. When the Neoplasm invade and destroy the surrounding tissue as it grows, it is called Malignant tumor or Cancer.

4. Malignant tumors release cells into the blood stream or into the lymphatic circulation. This spread of Neoplastic foci is called matastases . Tumors , both bening and malignant are named by appending – oma to the suffix of a term. Cancers formed by layers of cells are called carcinomas. Cancers formed from connective tissues or blood vessels are called sarcomas.

5. Cancers are named after the specific cell types affected e.g. hepatomas – cancer of liver hepatocytes . Carcinogenesis is a multi step process involving numerous genetic changes that consequently convert a normal cell into malignant type. Cancer – causing genes are called oncogenes Viruses associated with cancer or cancer initiation ( Neoplasia ) are called Oncoviruses/Oncogenic viruses. There are presently eight (8) replication defective o ncoviruses associated with human cancer.

6. Carcinogenesis (or more properly, oncogenesis ) is a complex, multistep process in which cellular transformation may be only the first, although essential, step along the way. Transformed cells have an altered phenotype, which is displayed as one (or more) of the following characteristics: 1. Loss of anchorage dependence: Normal (i.e., nontransformed ) adherent cells such as fibroblasts or epithelial cells require a surface to which they can adhere. In the body, this requirement is supplied by adjacent cells or structures; in vitro, it is met by the glass or plastic vessels in which the cells are cultivated. Some transformed cells lose the ability to adhere to solid surfaces and float free (or in clumps) in the culture medium without loss of viability.

7. 2. Loss of contact inhibition: Normal adherent cells in culture divide and grow until they have coated all the available surface for attachment. At this point, when adjacent cells are touching each other, cell division stops—the cells do not continue to grow and pile up on top of one another. Many transformed cells have lost this characteristic. Single transformed cells in a culture dish become visible as small thickened areas of growth called ‘transformed foci’ —clones of cells all derived from a single original cell.

8. 3. Colony formation in semi-solid media: Most normal cells (both adherent and nonadherent cells such as lymphocytes) will not grow in media that are partially solid due to the addition of substances such as agarose or hydroxymethyl cellulose; however, many transformed cells will grow under these conditions, forming colonies since movement of the cells is restricted by the medium. 4. Decreased requirements for growth factors: All cells require multiple factors for growth. In a broad sense, these include compounds such as ions, vitamins, and hormones that cannot be manufactured by the cell. More specifically, it includes regulatory peptides such as epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) that regulate the growth of cells. These are potent molecules that have powerful effects on cell growth.

9. Some transformed cells may have decreased or may even have lost their requirement for particular factors. The production by a cell of a growth factor required for its own growth is known as autocrine stimulation and is one route by which cells may be transformed. 5. Alteration in intracellular components and biochemical processes e.g. Nucleus, mitochondria, protein synthesis. 6. Possession of Viral Genome: Transformed cells contain either whole or part of the genome of the virus integrated into the cell DNA. 7. Chromosomal changes; such as karyotypes e.g. deletion, duplication etc. - After being transformed by viruses, many tumor cells contain a virus – specific antigen on their cell surface called Tumor -specific transplantation antigen (TSTA) or T-antigen.

10. 8. Morphological Change: Transformed cells are more elongated than, the normal cell, more refractile and randomly oriented. 9. Transformed cells are less – normal cells, with chromosomal abnormalities (No. Of chromosomes/fragmented chromosomes).

11. Viruses Associated With Human Cancers Family Virus Cancer Papillomaviridae Human papillomaviruses Genital tumors Squamous cell carcinomas Oropharyngeal carcinomas Herpesviridae Epstein-Barr virus Nasopharyngeal carcinoma African Burkitt’s lymphoma B cell lymphoma Hepadnaviridae Hepatitis B virus Hepatocellular carcinoma Retroviridae Human T lymphotrophic viruses Human immunodeficiency viruses Adult T cell leukemias AIDS-associated tumors (due to impaired T cell responses Flaviviridae Hepatitis C virus Hepatocellular carcinoma

12. 1. Human T- lymphotropic viruse 1 (HTLV 1) The Human T- lymphotropic viruses (HTLV) belong to Retroviridae family, genus Delta retrovirus . The human T- lymphotropic virus, or human T-cell leukemia -lymphoma virus (HTLV) family of viruses are a group of human retroviruses that are known to cause a type of cancer called  Adult T-cell L eukemia /Lymphoma (ATL)  and a diseases called HTLV-I Associated Myelopathy /Tropical Spastic Paraparesis (HAM/TSP)

13. HTLV-1 is transmitted sexually, vertically from infected mother, breastfeeding, parenterally , by contaminated blood and blood products transfusion, sharing of contaminated needles and syringes, or transplantation of infected organs and tissues

14. The primary target of HTLV 1 is adult CD4 T-cell and most infected individuals are asymptomatic. However, a significant number may develop persistent infection and progress to aggressive lymphoproliferative disease and Adult T-cell Leukemia/Lymphoma-ATLL

15. Symptoms of HTLV-I associated myelopathy Weakness in the legs that gets worse over time Numbness or tingling Stiff muscles Muscle spasms Bladder problems Constipation Double vision Deafness Coordination problems Tremors

16. 2. HIV – Kaposis sarcomas (Cancers of common tissue and blood vessels ). KAPOSIS SARCOMA

17. KAPOSIS SARCOMA AND HERPES ZOSTER IN HIV/AIDS

18. Human Herpes Virus Types 8: dsDNA , enveloped Kaposis sarcoma Herpes is a virus, specifically “ herpesvirus hominus ”. Simplex is a sub-category of that family. Simplex falls into five categories, types 1, 2, 6, 7, and 8. Generally type I infects the mouth in humans and type II affects the genital tract, but there is a substantial overlap. Type 6 and 7 cause an infection of infancy and Type 8 has been associated with Kaposi’s Sarcoma which is seen in HIV.

19. 3. Hepatitis C Virus (HCV) Etiologic agent of post transfusion and sporadic non-A, non-B hepatitis. Infects 2% of population world wide Associated with hepatocellular carcinoma (HCC) Causes active inflammation and fibrosis which progress to cirrhosis and ultimately lead to tumor development.

20. HEPATITIS C – HEPATOCELLULAR CARCINOMA

21. 4. Human Papillomavirus The over 70 viral types in the genus Papillomavirus are all involved in the etiology of benign tumors such as warts and papillomas , as well as malignancies, the latter mainly in the genital area (cervical carcinoma). These organisms cannot be grown in cultures. Diagnosis therefore involves direct detection of the viral genome and histological analysis. Serology is less important in this group. Pathogens. The papillomaviruses have a diameter of 55 nm and contain an 8 kbp dsDNA genome. There are two distinct regions within the circular genome: one that codes for the regulator proteins produced early in the replication cycle and another that codes for the structural proteins synthesized later. Over 70 papillomavirus types have been described to date, all of which induce either benign or malignant tumors in natural or experimental hosts.

22. Pathogenesis and clinical picture. Papillomaviruses infect cells in the outer layers of the skin and mucosa and cause various types of warts by means of local cell proliferation). Specific virus types correlate with specific pathohistological wart types. Plantar and vulgar warts, flat juvenile warts, and juvenile laryngeal papillomas apparently always remain benign. By contrast, the genital warts caused by types 6 and 11 ( condylomata acuminata ) can show carcinomatous changes. Of all papillomavirus -caused cervical dysplasias , 50% contain human papillomavirus (HPV) 16 and 20% HPV 18.

23. All wart viruses induce primary proliferation of the affected cells with large numbers of viruses found in the cell nuclei. Papillomaviruses possess oncogenes (E5, E6, and E7 genes) that bind the products of tumor suppressor genes: E6 binds the p53 gene product, E7 the Rb gene product

24. HPV GENITAL WARTS

25. HPV SKIN CANCER

26. HPV SKIN CANCER

27. HPV SKIN CANCER

28. 5. Epstein – Barr Virus (EBV) There is now epidemiological and/or molecular evidence that EBV infection is associated with at least five human tumours : 1. Burkitt’s lymphoma. 2. Nasopharyngeal carcinoma (NPC), a highly malignant tumour seen most frequently 3. B-cell lymphomas in immunosuppressed individuals (e.g., AIDS patients). 4. Some clonal forms of Hodgkin’s disease. 5. X-linked lymphoproliferative syndrome (XLP), a rare condition usually seen in males where infection with EBV results in a hyperimmune response in China.

29. There is a strong association between EBV and NPC. EBV is Ds-DNA, Mostly during childhood with significant symptoms. Post adolescent infection with EBV is self limiting lymphoproliferative disease. Replicates in the oral epithelial infecting the B – lymphocytes via the oral pharynx latently. BURKITT’S LYMPHOMA IN CHILDREN

30. 6. Hepatitis B Virus Pathogen The hepatitis B virus (HBV) is the main representative of the family of Hepadnaviridae . The name of the family is an acronym of the disease caused by the virus and its genomic type ( hepadnavirus = hepatitis DNA virus). It causes a sometimes chronic form of liver inflammation (hepatitis) and its genome consists of partially double-stranded DNA. The replication cycle of the HBV includes a transient RNA phase. The HBV possess an envelope made up of a cellular double lipid layer in which are integrated the hepatitis B surface (HBs) antigen, a 25 kDa polypeptide, and its precursor stages PreS1 (40 kDa ) and PreS2 (33 kDa ).

31. The HBV possess an envelope made up of a cellular double lipid layer in which are integrated the hepatitis B surface (HBs) antigen, a 25 kDa polypeptide, and its precursor stages PreS1 (40 kDa ) and PreS2 (33 kDa ).

32. Pathogenesis and Clinical Picture . The incubation period of hepatitis B is four to 12weeks, followed by the acute infection phase, icteric , or anicteric course, once again with a variable duration of two to 12 weeks. The hepatic cell damage resulting from an HBV infection is not primarily due to cytopathic activity of the virus, but rather to a humoral and cellular immune response directed against the virus-induced membrane antigens (HBs, HBc ) on the surface of the infected hepatocytes : 0.5–1% of those infected experience a fulminant , often lethal, hepatitis. In 80–90% of cases the infection runs a benign course with complete recovery and elimination of the HBV from the body. A chronic infection develops in 5–10%.

33. Risk factors -Primarily childbirth, person-to-person in early childhood, body piercings/tattoos, toiletries -Also sexually transmitted -Transmitted via infected blood, wet or dried -Each subtype has a different genome, and each genome is endemic to a different area

34. Three forms are differentiated, but mixed forms are possible: — healthy HBV carriers, — chronic persistent hepatitis (CPH) without viral replication, and finally — chronic aggressive hepatitis (CAH) with viral replication and a progressive course. A chronic infection can result in development of a carcinoma ( hepatocellular carcinoma, HCC) or cirrhosis of the liver, with incidence varying widely from one geographic area to another. The delta agent appears to have an unfavorable influence on the clinical course, usually making the disease more aggressive, increasing the number of complications and worsening the prognosis.

35. Diagnosis Hepatitis B is diagnosed by identifying the various HBV antigens or the antibodies directed against them. Both antigens and antibodies can be detected in patient blood using a solid phase test (enzyme immunoassay / ELISA). Antibody detection for IgG and IgM is diagnostic. Epidemiology and prevention Humans are the sole reservoir of HBV. Transmission is parenteral , either with blood or body fluids containing HBV (sexual intercourse) that come into contact with mucosa, lesions, or microlesions in the skin. In transmission by blood, the tiniest amounts contaminating syringe needles, ear-piercing needles, tattooing instruments, etc. suffice to produce an infection.

36. Hepatitis B infections from blood transfusions have been greatly reduced by thorough screening of blood donors for HBs antigens, despite which patients receiving multiple transfusions or dialysis remain a highrisk group. Another high-risk group includes all healthcare workers with regular blood contact. All blood samples must be considered potentially infectious and handled only with disposable gloves. Addicts who inject drugs with needles are also obviously exposed to a very high level of risk.