Viruses and cancer Flashcards
What are the two effects of viruses?
- can cause acute or chronic/persistant infections - SARS-CoV-2, EBV
- can cause cytopathic or non-cytopathic infections - influenza, HCV
What chronic virus infections are associated with cancer?
- HBV
- HCV (RNA virus)
- EBV
- HPV
- HTLV-1
What are the two ways in which chronic viral infections cause cancer?
- 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
Describe the Papilloma virus
- 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
Explain the life cycle of papillomavirus
- virus infects basal cell layer (cells are actively dividing)
- establish themselves as replicating pools
- as cells progress, they become more differentiated
How does cancer associate with integration of HPV into cellular chromatin?
- there are some hotspot of integration
- many integrations leads to up regulation of E6 and E7
What vaccines are used against HPV?
- HPV 16, 18 = cervarix
- HPV 16, 18 + 6, 11 = gardasil
- dramatic reduction in cervical carcinoma
Describe Polyoma virus : SV40
- 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
Describe the polyoma virus - JCV, BKV
- 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
What is Merkel cell polyoma virus?
- merkel cell polyoma virus causes brain tumours in hamsters
- merkel cell polyoma virus (MCV) recently associated with Merkel cell carcinoma (aggressive skin cancer)
Describe the lifecycle of a herpervirus
- 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
Describe EBV and KSHV/HHV-8
- rhadinoviruses
- other mammalian homologs (HVS, MRV)
- linear dsDNA genomes
- long unique region of 140kbp
- 85-100 ORFs
Cancer associated with EBV
- majority of people infected, some develop infectious mononucleosis-glandular fever
- rarely get : lymphoma in immunosuppressed patients, burkitts lymphomas (africa), nasopharyngeal cancer (asia)
Cancer associated with KSHV
- 1 in 40% of population infected causes a very mild fever
- rarely get : kaposi’s sarcoma, multi-centric castle-mans disease
How do EBV and KSHV establish latent infections of B cell precursor populations?
- 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