Viruses & Cancers Flashcards
What does cancer result from
Abnormal gene expression
What is a virus mechanism of action
Manipulate & interfere w/ gene expression in cells they infect to be able to replicate inside the cell & take control of cell & instruct to make new virions
What is the 5 links between viruses & cancer
Cancer prevalent at site of viral infection
Individual with caner have persistent viral infection
Cell tropism of virus is same as cell of origin of tumor
Viral nuclei acid in tumour cells
Cancer decrease in preventative measures are put in place to reduce incidence of viral infection
What is oncogenesis
Cancer is a multi step & multi chance process of genes before control over cell cycle is lost
Presence of virus is one event & requires another event to progress to malignancy
Why is it important to know what viruses caused cancer
To put preventative strategies into place
What are 5 ways of viral oncogenes
Inactivation of tumour suppressor proteins
Interference with programmed cell death
Interfere with cell senescence (telomerases)
Interference with DNA repair
Interfere with cell cycle control
What is direct oncogenesis
Virus infection evade immune response & persist long term by transforming the cell & proliferate. This disrupt repair mechanisms making DNA vulnerable to damage.
If exposed to carcinogens factors/Immunosupression it can lead to cancer
What is indirect oncogenesis
Not all cancer causing pathogens transform infected cell directly some cause cancer by persistence & chronic inflammation
DNA damage accumulate due to cell death & regeneration of infected cells
What is 2 examples of indirect oncogenesis
HCC due to chronic HBV & HCV
Gastric cancer due to H Pylori
Why does virus transform cells
Produce new viral proteins
How does viruses transform cells
Stimulate cell proliferation & as cell divide a copy of the virus genome is integrated into daughter cell forming transformed cell that multiply faster & immortal
What is a transformed cell
Altered morphology & genome instability
Loose contact inhibition & grow on top of each other
Why does transformation occur
To persist in the host & evade immune system
What cells does HPV infect
Epithelial surfaces where it causes proliferative lesions at site of inoculation
Basal epithelial where replication of DNA occur
What is the pathogenesis of HPV infection
Epithelial cells mature, production of structural viral proteins & virus particles are shed
Infected cell desquamate & viral genome is integrated into host DNA
Inactivate regulatory genes & increase proliferation of infected cell
How does Epstein Barr virus persist
Establish latent infection in B lymphocytes
What is Epstein Barr virus associated with
Rare malignant & pre-malignant disorders of B cells/epithelial cells
What are the normal life cycle of B cells
Short-lived cells made in the bone marrow & released into the blood & circulate through lymphoid tissue to find Ag that the B cell receptor recognize & if not they die
What is the life cycle of EBV infected B cell
Virus express number of genes that transform the B cell to become immortal & proliferate to pass virus on to daughter cell
How does EBV manifest in a healthy person
Kept in check by T cells but still carry EBV in B cells
How does EBV manifest in a immunosupressed person
B cell increase in number of cells & initially polyclonal then monoclonal malignancy
What is another factors that will increase B cell proliferation of EBV
Genetic abnormalities that accumulated
What is HTLV1 & what does it cause
Retrovirus
T cell leukaemia
What is the pathogenesis of HTLV1
Enzyme reverse transcriptase which converts RNA genome into DNA of T cells & virus integrate into host genomes & cause clonal expansion of infected cell by activating 2 oncoprotein Tax & HBZ
What is the complication of adult T cell leukaemia
Most asymptomatic
ATL
TSP
What cancer risk does HBV increase
HCC
What is HBV mechanism of oncogenesis
Indirect
Why does chronic HBV increase HCC risk
Ongoing immune mediated damage to liver with cycles of regeneration of liver cells & sensitized to effect of co-carcinogens
To what cancer to HCV predispose you to
HCC
What is the pathogenesis of HCV
RNA virus that does not transform infected cell but persist in host due to immune evasions tactics (replication & immune mediated damage to livers cells)
