复旦大学：《医学微生物学 Medical Microbiology（MBBS）》课程讲义_理论课_Lecture24-Herpesvirus & Human Cancer-associated Viruses

Herpesvirus Human Cancer associated viruses Qiliang Cai(蔡启良) MOH&MOE Key Lab of Medical Molecular Virology Shanghai Medical College, Fudan University (复旦大学上海医学院分子病毒学教育部/卫生部重点实验室) 2013-12-09

Herpesvirus & Human Cancer - associated Viruses Qiliang Cai (蔡启良) MOH&MOE Key Lab of Medical Molecular Virology Shanghai Medical College, Fudan University (复旦大学上海医学院分子病毒学教育部/卫生部重点实验室) 2013-12-09

Take-home messages 1. The purpose of viral life is to replicate itself (its associated L pathogenesis or human diseases are secondary effects) 2. Virus utilizes host machinery to replicate (cellular and organal) 3. The ultimate form of parasitization is to co-exist with the host. (at both individual and population levels) 4. Studies of viruses have double meanings (medically important and scientifically interesting) 5. Herpesvirus has two phases of the life cycle latent infection and lytic infection. 6. Which types of HPv are considered"high risk"that may cause pre-cancerous lesions and lead to cervical cancer?

Take-home messages: 1. The purpose of viral life is to replicate itself. (its associated pathogenesis or human diseases are secondary effects) 2. Virus utilizes host machinery to replicate. (cellular and organal) 3. The ultimate form of parasitization is to co-exist with the host. (at both individual and population levels) 4. Studies of viruses have double meanings. (medically important and scientifically interesting) 5. Herpesvirus has two phases of the life cycle: latent infection and lytic infection. 6. Which types of HPV are considered “high risk” that may cause pre-cancerous lesions and lead to cervical cancer?

Herpesvirus 1 Introduction of herpesviruses 2. Herpesviral latency 3. Mechanism of herpesviral replication 4. Oncolytic virotherapy Papillomavirus 1. Characteristics of HPv 2. Epidemiology of genital HPV infection 3. Pathogenesis, Clinical manifestations and sequelae 4. Diagnosis, Treatment Prevention

1. Introduction of herpesviruses 2. Herpesviral latency 3. Mechanism of herpesviral replication 4. Oncolytic virotherapy Herpesvirus Papillomavirus 1. Characteristics of HPV 2. Epidemiology of genital HPV infection 3. Pathogenesis, Clinical manifestations and sequelae 4. Diagnosis, Treatment & Prevention

Changes in cell that are at the roots of cancer Genetic and epigenetic alterations. (Proto-oncogene, tumor suppressor gene, mutator gene) V Mutations Deletions Recombinations Transpositions Epigenetic alterations(DNA methylation, imprinting Acquisition of VirAL genetic material

Changes in cell that are at the roots of cancer Genetic and epigenetic alterations: (Proto-oncogene, tumor suppressor gene, mutator gene) Mutations Deletions Recombinations Transpositions Epigenetic alterations (DNA methylation, imprinting) Acquisition of VIRAL genetic material

Virus←→3040% Human cancers EBV assoc, with Burkitts HTLV-1 and link Lymphoma Discovered to human T-Cell 1st Human Leukemia discovered Tumor Virus (1981) (1965) KSHV and link to Ks ALV HA∨ (1908) (1953-54) Merkel cell Link bet. HBV& Discovered MMTV Hepatocellular (1994) Polyoma Virus link to Merkel Cell Cancer RSV (1936) Carcinoma MPV 2008 (1911) (1953) (1975) Link bet. hcv CRPV SV40 Link bet. HPV& Hepatocellular FDA approves use HPV (1960) Cervical Cancer Carcinoma of HPv vaccine (1907) (1933) MLV (1951) (1974-1984) (1989) for cervical cancer (2006) 19101920193019401950196019701980199020002010 Timeline of Advances on Tumor Virology Javier.R.T et al. Cancer res 2008

Javier, R. T. et al. Cancer Res 2008 Virus  30-40% Human Cancers Timeline of Advances on Tumor Virology

(1966) (1976) (2008) Peyton Ross Baruch Blumberg Harald zur hausen Rous sarcoma virus Hepatitis B Virus Human Papilloma Virus (Rockefeller Univ) (Inst for Cancer Res (German Cancer Research Philadelphia) Centre, Heidelberg Nobel Prize Winners in Tumor Virology

Nobel Prize Winners in Tumor Virology

How do viruses contribute to Cancer? y Integrations that cause activation or inactivation of oncogenes or tumor suppressors(e.g RNA Viruses) y Expression of genes that alter key signal transduction pathways-this is our focus Chronic activation of inflammatory responses

7  Integrations that cause activation or inactivation of oncogenes or tumor suppressors (e.g. RNA viruses)  Expression of genes that alter key signal transduction pathways - this is our focus  Chronic activation of inflammatory responses How do Viruses Contribute to Cancer?

Why do viruses cause cancer? a Viruses and cancer cells have similar needs: Proliferation control Cell death control Modulation of immune response Induction of vascularization Metastasis(tumor) cell migration(viruses)

 Viruses and cancer cells have similar needs: • Proliferation control • Cell death control • Modulation of immune response • Induction of vascularization • Metastasis (tumor)/ cell migration (viruses) Why do viruses cause cancer?

Major human Oncogenic Viruses 口 DNA VIRUSES .Small dna tumor viruses - Adenovirus意 Hepatitis virus B(HBv) Human Papilloma virus(HPV Merkel cell polyma virus(MCV, JCv) .Herpesviruses(large) Epstein Barr virus(EBV Kaposis Sarcoma Herpesvirus( KSHv) 口 RNA VIRUSES Human T-cell Leukemia Virus 1(HTLV1) Hepatitis virus C(HCv HⅣ

 DNA VIRUSES •Small DNA tumor viruses - Adenovirus - Hepatitis virus B (HBV) - Human Papilloma virus (HPV) - Merkel cell polyma virus (MCV, JCV) •Herpesviruses (large) - Epstein Barr virus (EBV) - Kaposi’s Sarcoma Herpesvirus (KSHV)  RNA VIRUSES - Human T-cell Leukemia Virus 1 (HTLV1) - Hepatitis virus C (HCV) - HIV Major human Oncogenic Viruses - Human Papilloma virus (HPV) •Herpesviruses (large)

If you're infected, does this mean that you will get cancer? No! Viruses did not specifically evolve with the need to cause cancer-they simply have similar(but distinct needs Development of tumors almost always requires: Additional genetic alterations and/or Compromised host (e.g. immuno-suppression

• No!  Viruses did not specifically evolve with the need to cause cancer - they simply have similar (but distinct) needs  Development of tumors almost always requires: • Additional genetic alterations and/or • Compromised host (e.g. immuno-suppression) If you’re infected, does this mean that you will get cancer?