1. Viral Infection Detection

2. Clinical examinations & findings Antibody detection Electron Microscopic: SEM & TEM Molecular assays: PCR Detection of viral receptors Example: Hemagglutination & Hemagglutination inhibition Culture Plaque formation (PFU, Pock)

5. The Culture of Viruses 1.laboratory animals 2.Embryonated eggs 3.Cell lines (Tissue cultures) Primary cell culture Diploid cell lines Continuous cell lines Cytopatic effects (CPEs)

10. Cytopatic effects (CPEs): Cell lyses (degeneration) Aggregation Malignant transformation Giant cells Cell rounding Viral gene expression Loss of attachment (to culture dish) Cell-Cell fusion (Syncytial cells) Inclusion body: Negri body

11. Rabies Negri bodies

12. Syncytial cells by Respiratory syncytial virus (RSV)

13. herpes simplex virus (HSV) type 1-infected primary rabbit kidney cells CPE: rounding and detachment of cells

15. Adenovirus beta galactosidase

16. Viral genetics Virus - Virus interactions Viral cancers

17. Different interactions between two different viruses in a cell Recombination (based on Crossing over) - between HSV1 & HSV2 Reassortment - between Influenza viruses Complementation - Rescue of a lethal mutant with a defined genetic sequence of other virus Transcapsidation - Pseudoviruses

18. Cell transformation Changes in cellular growth, cellular morphology, antigenic compounds. Oncogenic viruses can be carcinogen (causing malignant tumors) and make cells to transform.

19. Tumor viruses Why some viruses are considered the causative of tumors? -Biological criteria for causal association of viruses with tumors: The presence of virus in tumor tissues The presence of virus before disease onset Viral persistence The location of virus at appropriate sites Prevention of the disease by prevention of viral infection

20. Human Oncogenic viruses Human Oncogenic RNA viruses Retroviruses: HTLV-1 & HTLV-2, HIV: Kaposi’s sarcoma Human Oncogenic DNA viruses Human Hepatitis B virus: Hepatocellular carcinoma Herpesviruses: Epstein-Barr virus: Burkitt’s Lymphoma/ Epstein-Barr virus: Nasopharyngeal Carcinoma Herpesviruses: Herpes Simplex virus Type 2: Cervical intraepithelial neoplasia Herpesviruses: Human Cytomegalovirus: Cervical tumors/ Human Papillomaviruses: types 18, 16, 33: Cervical cancer

21. Viral and hast genes involved in cancers Virus: Promoter genes (viral oncogenes= v-onc ) Host: Tumor Repressor Genes Oncogenes (cellular oncogenes= c-onc)

22. Tumor Repressor Genes (Anti-oncogenes) They are normally oncogene regulators. If repressed (e.i. by a virus promoter)  Activating the relevant oncogene  Causing oncogene products  Cell transformation

23. Cellular Oncogenes (c-onc genes) Normally inactivated. If disregulated or mutated, then causes transformation in the cell by oncogene products.

24. Example: Retinoblastoma (Rb) gene is one of these tumor repressor genes which regulates the pass of the cells to S stage of the cell cycle. Mutation of Rb gene by some viral promotors transforms the cell.

25. Growth factors Signaling proteins DNA binding proteins and other regulatory proteins Cellular receptors