Papilloma and Polyomaviruses: T Transformation and Cancer f ti d - - PowerPoint PPT Presentation

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Papilloma and Polyomaviruses: T Transformation and Cancer f ti d - - PowerPoint PPT Presentation

Aug 20, 2022 15 likes •420 views

Papilloma and Polyomaviruses: T Transformation and Cancer f ti d C Harvey L. Ozer, M.D. Professor Dept. of Microbiology and Molecular Genetics Director, NJMS-UH Cancer Center , Contact information: ozerhl@umdnj.edu @ j Cancer Center

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Papilloma and Polyomaviruses: T f ti d C Transformation and Cancer

Harvey L. Ozer, M.D. Professor

  • Dept. of Microbiology and Molecular Genetics

Director, NJMS-UH Cancer Center ,

Contact information: ozerhl@umdnj.edu @ j Cancer Center H1210, Tel: 2-3558

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Papovaviruses

1. Classification: Polyoma, SV40, papilloma viruses 2. Historical perspective: SV40 as a probe for cellular functions 3 Host range: replication and “transformation” 3. Host range: replication and transformation 4. Role of multifunction early viral proteins and transformation 5. Are papovaviruses human tumor viruses

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Papovaviruses p

Classification: Polyoma, SV40, papilloma viruses

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Papovaviruses Papovaviruses

Polyoma Viruses Papilloma

C ? * *

200

SV40 (primate) JC,BK (human) Py (mouse) MCPyV (human) HPV cutaneous Multiple species HPV 6,11 CD HPV 16,18 CIN

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Papovaviruses p

Historical perspective: SV40 as a probe for cellular functions

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  • 1. Risk of primary cell sources (AGMK)

Historical perspective

  • 2. Definition of specificity of restriction sites (Nobel Prize)

3. First sequenced genome 4. Deletion mutants and functional map (colinearity) 5 Probe for host functions

  • 5. Probe for host functions
  • a. Nuclear localization signal
  • b. (Confirmed) splicing
  • c. Identification of enhancer sequences (Py, SV40)

d D l t f i it DNA li ti

  • d. Development of in vitro DNA replication
  • e. co-IP –Rb, p53, others

6. Model of a DNA tumor virus

  • a. Role of viral ts (tsA) mutants
  • a. Role of viral ts (tsA) mutants
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Host Range: Replication and “Transformation”

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Papovaviruses

Host range: replication and “transformation”: SV40 permissive infection = lytic/monkey cell SV40 non-permissive infection = transformation/mouse 3T3 cells SV40 non permissive infection transformation/mouse 3T3 cells SV40 (semi-permissive) infection = lytic vs transformation/human diploid fibroblasts Role of temperature-sensitive (ts) mutants Papillomaviruses (HPV) and cell differentiation Papillomaviruses (HPV) and cell differentiation

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Papovaviruses

Host range: replication and “transformation”: SV40 permissive infection = lytic/monkey cell

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Papovaviruses

Host range: replication and “transformation”: SV40 non-permissive infection = transformation/mouse 3T3 cells Intergration of viral genome SV40 (semi-permissive) infection = lytic vs transformation/human diploid fibroblasts Role of temperature-sensitive (ts) mutants

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SVtsA/3T3 SV/3T3 37o 33oC 37o 33oC Cell Number confluent confluent Time in days Time in days confluent co ue t

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Papovaviruses

Papillomaviruses (HPV) and cell differentiation

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Role of Multifunction Early Viral Proteins and Transformation

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Papovaviruses

Role of multifunction early viral proteins and transformation: Inactivation of cell growth suppressor What is pRb What is pRb What is p53 Different strategies to a common end SV40 early region (T,t), telomerase, (Sen6) and mutant ras (Hahn and Weinberg)

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Comparison of HPV

low high i l i l cervical cervical cancer cancer genome 6, 11 16, 18 53 l l l l p53 level normal low ubiquitin E2 no yes DNA status episomal integrated telomerase no induced

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Are Polyomaviruses (esp. SV40) DNA tumor viruses y ( p )

  • r Why is there still uncertainty about SV40 and mesotheliomas
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Papovaviruses

Are papovaviruses human tumor viruses: Are papovaviruses human tumor viruses: HPV and cervical carcinogenesis (Zur Hausen) human anti HPV vaccine (Gardasil, Cervarix) SV40 and mesothelioma/other – controversy (Handout) SV40 and mesothelioma/other – controversy (Handout) Carbone et al. Oncogene 9:1781-1790 (1994) Other? Feng et al. [Merkel Cell Carcinoma], Science 319:1096-1100 (Feb 22, 2008)

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Papovaviruses

1. Classification: Polyoma, SV40, papilloma viruses 2. Historical perspective: SV40 as a probe for cellular functions

  • 3. Host range: replication and “transformation”:

SV40 permissive infection = lytic/monkey cell SV40 non-permissive infection = transformation/mouse 3T3 cells Intergration of viral genome SV40 (semi-permissive) infection = lytic vs transformation/human diploid fibroblasts Role of temperature-sensitive (ts) mutants Papillomaviruses (HPV) and cell differentiation Papillomaviruses (HPV) and cell differentiation 4. Role of multifunction early viral proteins and transformation Inactivation of cell growth suppressor What is pRb 3 What is p53 Different strategies to a common end SV40 early region (T,t), telomerase, (Sen6) and mutant ras (Hahn and Weinberg) 5. Are papovaviruses human tumor viruses 5. Are papovaviruses human tumor viruses HPV and cervical carcinogenesis (Zur Hausen) human anti HPV vaccine (Gardasil, Cervarix) SV40 and mesothelioma/other – controversy (Handout) Carbone et al. Oncogene 9:1781-1790 (1994) Other? Other? Feng et al. [Merkel Cell Carcinoma], Science 319:1096-1100 (Feb 22, 2008)