Viruses and Cancer Flashcards
(37 cards)
1
Q
What did Peyton Rous discover?
A
- Chicken Sarcoma Virus in 1909
- Tumours found in the muscles of chickens which are transmissible by viruses
2
Q
How did he discover chicken sarcoma virus?
A
- Removed sarcoma from the breast of a chicken
- Broke it up into small chunks of tissue
- Ground it with sand
- Passed it through a fine pore filter to collect filtrate
- Injected filtrate into young chickens
- Observed sarcoma in injected chicken
3
Q
What is rous sarcoma virus?
A
- a retrovirus which has an extra gene called SRC
- Causes sarcoma in chickens
4
Q
What is the difference between a DNA virus and a retrovirus
A
A DNA virus injects its own DNA into a host cell straight into the genome, however a retrovirus is a type of RNA virus which has RNA that needs to be reverse transcribed into DNA before it can enter the genome
5
Q
What is an acute/chronic virus?
A
- Acute = occur suddenly and either resolve quickly or result in death
- Chronic = persists over a long period of time (6+ months)
6
Q
Give an example of an acute and a chronic virus
A
- Acute = SARS-CoV2 (Covid)
- Chronic = Human Immunodeficiency Virus (HIV)
7
Q
What is a cytopathic/non-cytopathic viru
A
- Cytopathic = either completely eliminated by the immune system or they kill the infected organism
- Non-cytopathic = can establish long-lasting infections and successfully evade complete destruction by the immune system
8
Q
Give an example of a cytopathic and a non-cytopathic virus?
A
- Cytopathic = influenza virus
- Non-cytopathic = Hepatitis C virus (HCV)
9
Q
What are examples of chronic virus infections associated with human cancer?
A
- Hepatitis B virus (HBV)
- Hepatitis C virus (HCV) (RNA virus)
- Epstein Barr virus (EBV)
- Human herpes virus-8 (HHV-8)
- Human papilloma virus (HPV)
- Human T cell lymphotropic virus (HTLV-1)
- Polyoma virus
10
Q
What are 2 ways in which chronic viral infections cause cancer?
A
- Immortalisation of cells followed by secondary mutation due to DNA damage
- Chronic inflammation leading to multiple cycles of tissue repair
11
Q
What is immortalisation?
A
The ability of a cell line to reproduce indefinitely. The cells escape from the normal limitation of a finite number of division cycles which can lead to tumour formation
12
Q
What percentage of human cancers are associated with viral infections?
A
- Approx 40%
- specifically liver and cervical cancers and Lymphomas
13
Q
What did Hansen discover between HPV and cervical cancer?
A
- Cervical carcinoma lesions derived from benign lesions are histologically similar to warts and other papillomas
- Found that HPV DNA is found within cervical carcinomas
- Now it’s known that approx 80-90% of cervical cancers are associated with HPV16 and/or HPV18
14
Q
What are some characteristics of HPV?
A
- Known to consist of 150+ genotypes
- Sexually transmitted
- Some of these genotypes (eg HPV16/HPV18) are associated with cervical cancer
- Some are associated with warts of specific tissues
15
Q
What are some cancers that oncogenic HPV is associated with?
A
- Anogenital
- Oropharyngeal
- Oesophageal
16
Q
How does HPV cause cancer?
A
- Causes cells to undergo change and if they’re not treated they can, over time, become cancer cells.
- Once oncogenic HPV infects cells, it interferes cell communication, causing infected cells to multiply in an uncontrolled manner leading to tumours
17
Q
How does HPV infiltrate the body?
A
- Virus infects a basal keratinocyte in the epidermis with the use of early (E) genes
- The virus and cells replicate together
- Viral DNA is amplified in non dividing cells
- Using late (L) genes, the virus is made ready for infection of the individual
18
Q
What vaccines are there to protect from HPV?
A
- Cervarix -> HPV16/18
- Gardasil -> HPV16/18/6/11
- Has lead to a large reduction in cervical cancer
19
Q
Does SV40 polyoma virus cause cancer in humans?
A
- Simian virus 40 (SV40) is a type of Polyoma virus
- Infects monkeys and causes cancer in hamsters
- In US 1955-1963 90% children and 60% adults were inoculated with SV40-contaminated polio vaccines
- However there were no epidemiological links to cancer
- SV40 does infect human lung mesothelial cells, not sure if it causes mesotheliomas
20
Q
Do JCV/BKV polyoma viruses cause cancer?
A
- Both cause brain tumours in hamsters
- Both infect nearly all humans by 11 years
- JCV can cause progressive multifocal leukoencephalopathy (PML) seen in AIDS
- JCV is associated with astrocytomas that arise in JCV-PML lesions
- Both cancers are very rare
21
Q
Does MCV polyoma virus cause cancer?
A
- Merkel cell polyoma virus (MCV) causes brain tumours in hamsters
- Recently associated with Merkel cell carcinoma (aggressive skin cancer)
22
Q
What are human herpes viruses (HHVs)
A
- 8 different viruses that all infect humans
- Lifelong infections which are controlled by immunity
- Are latent/reactivating = able to lie dormant in the cell for a period of time with no symptoms and then become reactivated and cause infections
23
Q
What are the 8 HHVs?
A
- Herpes simplex virus type 1 (HHV-1)
- Herpes simplex virus type 2 (HHV-2)
- Varicella zoster virus (HHV-3)
- Epstein-Barr virus (HHV-4)
- Cytomegalovirus (HHV-5)
- Human herpesvirus 6 (HHV-6)
- Human herpesvirus 7 (HHV-7)
- Human herpesvirus 8 (HHV-8)
24
Q
What is an example of symptoms caused by HHV-3?
A
Causes chicken pox in early life and then shingles in later life
25
What is the life cycle of a HHV?
1. Virus enters and infects cell
2. Virus replicates inside the cell
3. Lytic infection causes the cell to die and the newly made viruses are released
4. Process repeats
26
How does HHV become latent?
A HHV establishes latency inside a new cell by:
- It replicates closely to the host genome and only uses proteins it really needs
- This results in not many viral antigens being displayed on the cell surface
- The virus is then able to avoid immuno surveillance and replicate for years
- It can then reactivate and continue its usual life cycle
27
What are characteristics of EBV and HHV-8?
- Both gamma-herpes viruses
- Both linear dsDNA genomes
- long unique region of 140 kbp
- 85-100 ORFs
28
What are cancers associated with EBV?
- majority of people are infected but most don’t develop anything further
- there are rare cancers developed:
1. Lymphoma in immunosuppressed patients (HIV/transplant)
2. Burkitt’s lymphoma in Africa
3. Nasopharyngeal cancer is Asia
29
What are cancers associated with HHV-8?
- up to 40% of populations infected usually only causing a mild fever
- rare cancers include:
1. Kaposi’s sarcoma
2. Multi centric Castelman’s disease
3. Primary effusion lymphoma (PEL)
30
How do EBV and HHV-8 become latent?
- both can immortalise peripheral B cells
- they convert these cells into immortalised lymphoblastoid cells
- HHV-8 can also infect and immortalise keratinocytes, epithelial cells and vascular endothelial cells
- latent infection only requires a fraction of the viral genome to be expressed
31
How do EBV and HHV-8 cause Burkitt’s lymphoma?
- the immortalised lymphoblasts made by the virus continue to divide, making them prone to picking up secondary mutations
- this is a problem for these cells as B cells have a potent recombinase system which allows them to perform chromosomal rearrangements and translocations
- an overexpression of this causes translocations that result in the formation of oncogenes
- Burkitt’s lymphoma is an example of this as a common translocation is bringing c-myc (ch8) next to an IgG loci (ch14) leading to the dysregulation of c-myc and its transformation into an oncogene
32
How does HHV-8 cause skin cancer?
- vascular endothelial cells can be infected by HHV-8 which triggers their transformation into spindle cells
- HHV8 latently infect VE cells
- HHV8 uses ephrin receptor A2, which is expressed on VE cells, that result in ligation that triggers angiogenesis and transformation
- These lytically infected cells induce host production of paracrine factors which, with virus-encoded factors, promote proliferation of latently-infected cells, invasiveness and angiogenesis
33
What is viral hepatitis?
- An infection that causes liver inflammation
- associated with several pathogens (Hepatitis A/B/C/D)
- often acute infections, resolved by host immunity
- sometimes chronic infections, kept under control by host immunity
- chronic infections can lead to cirrhosis and eventually hepatic cancer
34
What is Hepatitis B virus (HBV)
- A DNA virus
- it is chronic hepatitis that leads to cirrhosis and can eventually progress to hepatocellular cancer (HCC)
- one of the most common malignancies in the world, especially Africa and Asia
35
How successful is the HBV vaccine?
- In Taiwan, carrier rate in children fell from 10% to 1.3% 10 years after mass vaccination
- HCC rate is falling and is expected to decrease by 85% within 3-4 decades of mass vaccination
36
What is Hepatitis C virus (HCV)?
- an RNA virus (ssRNA flavivirus)
- causes chronic hepatitis
- no vaccine at the moment
- good drugs to protect but are expensive
- non-Cytopathic
- associated with extensive liver infiltration of leukocytes
- associated with generation and infiltration of CD8+ cells which attack and destroy infected cells
- HCV persistence is due to variants which are not recognised by CD8+ cells
37
What is human T-cell lymphotropic virus (HTLV-1)
- an RNA virus (retrovirus)
- isolated from adult T—cell leukaemia (ATL)
- varies from smouldering leukaemia to aggressive lymphoma
- inserts randomly and is able to transactivate the hosts oncogenes to immortalise T cells and induce leukaemia/lymphoma
- less than 1 in 100 infected in a lifetime
