Viruses and cancer Flashcards

1
Q

What are the two effects of viruses?

A
  • can cause acute or chronic/persistant infections - SARS-CoV-2, EBV
  • can cause cytopathic or non-cytopathic infections - influenza, HCV
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2
Q

What chronic virus infections are associated with cancer?

A
  • HBV
  • HCV (RNA virus)
  • EBV
  • HPV
  • HTLV-1
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3
Q

What are the two ways in which chronic viral infections cause cancer?

A
  • immortalisation followed by secondary mutation due to DNA damage
  • chronic inflammation leading to multiple cycles of tissue repair
  • 40% of cancers associated with viral infections
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4
Q

Describe the Papilloma virus

A
  • HPV known to consist of > 150 genotypes
  • some of these are associated with cervical cancers - HPV16 and 18
  • some are associated with warts of specific tissues
  • the ‘oncogenic’ HPVs are also associated with anogenital, oropharyngeal and oesophageal cancers
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5
Q

Explain the life cycle of papillomavirus

A
  • virus infects basal cell layer (cells are actively dividing)
  • establish themselves as replicating pools
  • as cells progress, they become more differentiated
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6
Q

How does cancer associate with integration of HPV into cellular chromatin?

A
  • there are some hotspot of integration

- many integrations leads to up regulation of E6 and E7

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7
Q

What vaccines are used against HPV?

A
  • HPV 16, 18 = cervarix
  • HPV 16, 18 + 6, 11 = gardasil
  • dramatic reduction in cervical carcinoma
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8
Q

Describe Polyoma virus : SV40

A
  • infects monkeys , causes tumour in hamsters
  • no epidemiological link to cancer
  • SV40 infects human lung mesothelial cells; viral DNA found in mesotheliomas, unclear whether it is in any way causal
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9
Q

Describe the polyoma virus - JCV, BKV

A
  • JCV, BKV cause brain tumours in hamsters
  • JCV and BKV infect nearly all humans by 11 years
  • JCV cause progressive multifocal leukoencephalopathy (PML) seen in AIDS and other immune suppressed states
  • JCV is associated with astrocytomas that arise in JCV-PML lesions
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10
Q

What is Merkel cell polyoma virus?

A
  • merkel cell polyoma virus causes brain tumours in hamsters

- merkel cell polyoma virus (MCV) recently associated with Merkel cell carcinoma (aggressive skin cancer)

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11
Q

Describe the lifecycle of a herpervirus

A
  • in primary infection, virus infects the cells, virus replicates, cells die = releases new virus
  • new virus attempts to establish cell
  • at some point immune system destroys virus and cells which express viral antigens
  • viruses are able to establish latency
  • one viral particle will establish itself in a cell and replicate in episome - low copy number
  • avoiding immunosurveilance, not presenting many antigens
  • can stay for years - immortalise cells its in
  • continually regenerate = latency
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12
Q

Describe EBV and KSHV/HHV-8

A
  • rhadinoviruses
  • other mammalian homologs (HVS, MRV)
  • linear dsDNA genomes
  • long unique region of 140kbp
  • 85-100 ORFs
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13
Q

Cancer associated with EBV

A
  • majority of people infected, some develop infectious mononucleosis-glandular fever
  • rarely get : lymphoma in immunosuppressed patients, burkitts lymphomas (africa), nasopharyngeal cancer (asia)
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14
Q

Cancer associated with KSHV

A
  • 1 in 40% of population infected causes a very mild fever

- rarely get : kaposi’s sarcoma, multi-centric castle-mans disease

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15
Q

How do EBV and KSHV establish latent infections of B cell precursor populations?

A
  • EBV and KSHV can both immortalise peripheral B cells
  • converts peripheral B cells into immortalised lymphoblastoid cells
  • KSHV can also infect and immortalise keratinocytes, epithelial cells and vascular endothelial cells
  • latent infection requires only a fraction of the viral genome to be expressed
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16
Q

Why do EBV and KSHV cause cancer?

A
  • the continued division of virally immortalised lymphoblasts = prone to pick up secondary mutations. Especially a problem in B cells since these express a potent recombinase system and chromosomal rearrangements and translocations
  • common translocation in Burkitts lymphoma is bringing c-myc next to an IgG loci on ch14 leading to dysregulation of c-myc = oncogene
17
Q

Why does KSHV cause skin cancer?

A
  • vascular endothelial cells can be infected by HHV8 trigger transformation to spindle cells
  • HHV-8 will latently infect VE cells
  • HHV-8 uses the ephrin receptor A2, expressed on VE cells
  • minority of HHV08 infected cells support lytic infection, albeit often abortive
  • lytically infected cells induce host production of paracrine factors (VEGF) which together with virus-encoded factors promote proliferation of latently infected cells, invasiveness and angiogenesis
18
Q

Describe viral hepatitis

A
  • associated with several pathogens called hepatitis virus A, B , C and D
  • often acute infections, resolved by host immunity
  • sometimes chronic infections, kept under control by host immunity
  • chronic infections can leads to cirrhosis and eventually hepatic cancer
19
Q

Hepatitis B virus and liver cancer

A
  • HBV is a DNA virus
  • chronic hepatitis followed by cirrhosis can progress to hepatocellular carcinoma
  • liver cancer - hepatocellular cancer
  • once of the most common malignancies in the world mainly in asia and africa
20
Q

Describe the hep b vaccine

A
  • in taiwan carrier rate in children fell from 10% to 1.3% 10 years after mass vaccination
  • already rate of HCC is falling and is expected to decrease by 85% within 3-4 decades of vaccination
21
Q

Hepatitis C virus and liver cancer

A
  • causes chronic hepatits/hepatoma
  • no vaccine at present
  • good drugs against HCV, but expensive
22
Q

Describe the immunopathology of hepatitis c

A
  • chronic hepatitis is a disease of severe liver damage and loss of hepatocytes
  • HCV is non-cytopathic
  • hepatitis associated with extensive liver infiltration of leukocytes
  • viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them
  • HCV persistence is associated with the generation of HCV variants that are not recognised by CD8+ cells
23
Q

Human T-cell lymphotropic virus

A
  • HTLV-1 isolated from adult T-cell leukaemia (ATL) a recent condition diagnosed in Japan in 1973
  • ATL varies from smouldering leukaemia to aggressive lymphoma involving visceral and skin lesions
24
Q

Describe the pathogenesis of HTLV-1

A
  • inserts randomly and is able to transactivate the hosts oncogenes and hence immortalise T cells to induce leukaemia and lymphoma