3. Virus Oncogenesis Flashcards
Are viruses organisms?
No, they are non living
Can viruses reproduce without a host cell?
No
What does a complete virus consist of?
Nueclocapsid
- Genome
- Capsid (composed of capsomeres) Envelope
- Membrane
- Ligands
What is the typical size of a virus?
10 - 300nm
What shape can a virus be?
Helical
Polyhedral
Complex (Binal0
What is an oncovirus?
A virus that can cause cancer
How many oncoviruses are recognised by WHO IARC?
6
What % of human cancers are caused by infection?
18%
12% are virus infections
Where do viruses rate on the risk factors for developing cancer?
2nd, just after tobacco usage
When/where/what was the first oncovirus discovered?
1908
University of copenhagen
Caused leukaemia in chickens
When was the first human oncovirus discovered?
1964
EBV
What was the most recent form of oncovirus discovered?
Merkel Cell Polyomavirus
2008
How do oncoviruses primarily cause cancer?
Deregulation of pathways involved in control of cell proliferation
DNA tumour viruses replicate where?
Nucleus
RNA tumour viruses replicate where?
Cytoplasm
What does the lytic life cycle consist of?
Replication
Lysis
Progeny virions
Generally do not cause cancer
What does the latent life cycle of a virus consist of?
VIrus
Cell
Integration (integrates into host genome)
Transformation
What is the difference between lytic life cycle and latent (lysogenic) life cycle?
In the latent life cycle, virus genome is integrated into host genome
What is transformation?
Viral genes interfere with control of cell replication and other aspects of cell phenotype
Loss of growth control
Reduced adhesion
Motility
Invasion
Can both DNA and RNA viruses transform cells?
Yesum
What is an oncogene?
A gene that can transform a normal cell to a malignant one
What is a viral oncogene?
Oncogene transmitted by virus
What is a proto-oncogene?
A normal gene that can become an oncogene
Are generally positive growth regulators
How many proto-oncogenes have been identified?
~70
What are anti-oncogenes?
Tumour supressor genes
What are some tumour supressor genes?
p53
Retinoblastoma protein (Rb)
What do tumour supressor genes do?
Regulate cell cycle
Apoptosis
Genomic stability
When cell is damaged, they arrest cell cycle for repair
Or apoptosis
What is p53s negative regulator?
mdm2
What are the known cancer viruses and what is their associated cancer type?
How many serotypes of HPV exist?
over 100
How is infection of HPV transmitted?
Sexual or close contact
What does HPV infect?
Skin epithelial cells and mucous membranes
What is the structure of HPV?
Non-enveloped
Icosahedral
Circular ds DNA
8kb genome size
Encodes 9 genes
What does HPV 6 and 11 cause?
Warts (benign)
What does HPV 16&18 cause?
Cancer
Cervical, uterine, vulvar, penile, anal, laryngeal
What do E6 and E7 genes of the HPV genome code for?
Proteins that inactivate tumour supressor proteins p53 and Rb
HPV, L1 gene codes for?
Protein that self assembles into shell
What are empty capsids called?
Virus like particles
Form base for HPV vaccines
What % of people will clear cervical HPV infection in 2 years?
90%
How does HPV progress to cancer?
Persistant infection Leads to cancer
E6 and E7 integration
Does smoking, age of first intercourse, contraception use, genetics influence HPV progression?
Yes
What does the HPV vaccine protect against?
Released in 2006
70% of cervical cancer
90% of genital warts
What is the structure of Herpesviridae?
Evnveloped
Icosahedral
Linear dsDNA
180kb genome
Contains Tegument for viral defence
What does Herpesvirus type 8 cause?
Kaposi’s sarcoma associated herpes virus
Causes Kaposi’s sarcoma (skin cancer)
What cell type does herpes 8 / HSHV infect?
B Lymphocytes
Is herpes 8 / KSHV linked to HIV infection?
Yes
What region is Herpes 8 / KSHV prevalent?
Africa, Mediterranean, Eastern Europe
How does Kaposi’s sarcoma infect aids patients?
Reks em when immune system is supressed
What family does the EBV (epstein barr virus) belong to?
Herpes 4
What cell type does EBV infect?
B - cells and Epithelial cells
How does EBV spread?
Oral transfer of saliva
What diseases does EBV cause?
Burkitts lymphoma
Hodkins lymphoma
Nasopharyngeal carcinoma
B cell lymphoma
X-linked lymphoproliferative disease (Duncans)
How does EBV cause Burkitts lymphoma genetically?
8:14 translocation at q32
What cell type does HBV infect?
Hepatocytes
What cancer does HBV cause?
Hepatocellular carcinoma
What is the structure of HBV?
Enveloped
Spherical
42nm diameter
dsDNA circular
How many proteins does HBV encode?
7 proteins
How is HBV transmitted?
Sexual contact
Blood
Maternal
Is there a vaccine for HBV?
Yes
What type of virus is HCV?
Flaviviridae
What cell type does HCV infect?
Hepatocytes
What is the structure of HCV?
Enveloped
Spherical
Linear ssRNA
How is HCV transmitted?
Sexual contact
Blood
Maternal
Neonatal
What is HCC?
Hepatocellular carcinogenesis
One of worlds most common and deadly cancers
Can HBV and HCV cause chronic and acute inflammation?
Yes
What type of virus is Merkel cell polyoma virus (MCV)?
Polyoma virus
What does Merkel Cell polyoma virus cause?
Merkel cell carcinoma (skin cancer)
Rare and aggressive
What is the structure of Merkel cell polyoma virus?
Non-enveloped
Icosahedral capsid
Circular dsDNA
Associated with cellular histones
How many proteins does Merkel cell polyoma virus encode?
5-9 proteins
Who does MCV typically effect?
Elderly and immunosupressed
What is Human T-cell leukaemia?
HTLV-1 is a retrovirus which causes Adult T-cell leukaemia
ATL (Clover like lymphocytes)
Infects CD4 T cells
What is the structure of HTLV-1?
Enveloped
Spherical capsid
Linear dimeric ssRNA
How is HTLV-1 transmitted?
Sexual contact
Blood
Maternal - neonatal
What % of HTLV-1 infected individuals develop ATL?
6%
How long is the incubation of HTLV-1?
30-40 years
What viral protein is activated in HTLV-1 infection?
Tax protein leads to uncontrolled proliferation
