Viruses And Cancer Flashcards
Oncoviruses
Retro rna Flavi rna Hepadna dna Papilloma dna Herpes dna Pox dna
(Adeno and polyo only in experimental animals not in actual host)
Rna oncovirus mech
All med directly or indirectly by oncogenes with cellular origin and no role in cell life cycle
Dna oncovirus mech
Transforming genes play essential roles in viral growth and are true biral genes with no cellular homologue
Action mech reflect role in viral cycle
Virus interaction to cause carcinogenesis
A multi stage process
Virus nah interact with cell factors to induce a cell into full transformation or virally induced benign tumour acted upon by other factors to induce malignancy
General characteristics defining cells transformed by tumour viruses
Altered cell morphology
Incr growth potential
Presence of viral DNA seq and virus-spec tumour assoc antigens
Chromosomal abnormalities
Retrovirus cell transformation mech
Convert RNA genome to DNA through reverse transcriptase
Dna genome then inserted into host genome where it can induce the cell to transform
Can transform cell by mechanisms: insertional mutagenesis, transduction (very rarely trans-activation)
Retro virus RNA v DNA struct
DNA has long terminal repeats on both ends
Both have 3 common genes GAG, Pol, Env
Insertional mutagenesis
Integrate next to cellular proto-oncogene so that this cell gene is now in control of the viral long terminal repeat, instead of being under its normal close tight transcriptional control
Long terminal repeat is either an enhancer or a promoter so makes transcription more likely
Insertion process is random so not every virus integrate next to oncogene hence variable time to form tumour
Known as slow transforming viruses due to random insertion
Transduction
Viruses carry a vONC in most cases it has replaced part of a viral struct pro so virus is defective and req a non defective helper virus to repl (exception is rous sarcoma virus that carries intact envelope and onc gene so is fully repl comptetent)
Fast transforming viruses as no lag between infection and tumour formation. vONC originate by cellular gene transduction
Transduction
V onc aquisition mech
Not fully known
Integration of viral genome into host chrom and encapsidation of rna part viral, part cellular with resulting recomb
During viral repl rounds mutation of oncogenesonit becomes more active or less affected by cellular control mechs. Also due to expression under LTR influence causes uncontrolled expr and pro activation.
Oncogene is part of viral genome and expr in every affected cell
Acute transforming viruses found
Rarely in nature suggesting each isolate is a new recomb
Not naturally transmitted between hosts perhaps as they are defective and because theyre so rapidly oncogenic so string selection against natural persistence by transmission
Trans activation (BLV eg)
In addition to normal genes, the viruses possess additional genes, at least one of which is tax (involved in trans activation of viral and cellular genes)
Viral integration - prod tax, expr of several cellular genes is upreg, nit conseq of LTR as integr is random and the same genes are always upreg most significantly IL2 and IL2rec genes involved in t cell act and prolif, so ATL cells have incr IL2rec on surf and grow and prolif without exogenous IL2
EBL pathogenesis
Chronic disease
Absence of chronic viremia, a long latent period and a lack of preferred viral integr sites
BLV is poorly infective and infection occurs via infected cells derived from an infected donor with persistent lymphocytes.
Shed in milk and urine, infection usually horiz. Iatrogenically infected by biting insects and needles
Transplacental transmission can occur
Endogenous retroviruses
0.5-1% of mammalian genome contains seq with proviral struct that behave as normal mendelian genes
They possess LTR GAG POL and ENV genes but are normally transcriptionally silent and often contain mutations within the structural genes and so are defective. Usually non pathogenic
Can recomb with exogenous viruses to gen new maybe virulent strains
Hypothesised that endogenous viruses may play a role in foetal dev (one in sheep has been shown to be essential in allowing normal placentation and so pregnancy)
Endogenous murine mammary tumour virus
Only known pathogenic endogenous virus
Inheritance if it gives rise to significant incidence of mammary carcinoma.
FeLV
Infection usually via saliva
Some cats prod neutr Ab and elim, others remain latently infected and some become persistantly infected and dev virus induced neoplastic and nonneoplastic dis
Outcome dep on age at exposure and dose and if it is endemic/repeat exposure
FeLV subgroups
A B and C
Due to polymorphism in an envelope glycopro, gp70, highest divergence level in region that interacts with rec. in infected cell gp70 blocks viral rec prev further infection by same sub group
A is antigenically stable and tropic for feline cells only
B and c dep on a for transmission
FeLV subtype assoc with dis
A essential for transmission
B present in most isolates assoc with high rate of persistent infection and so dis and leukaemia
C is rare inducing rapidly fatal red cell aplasia
Cats have a familu of endogenous biruses related to FeLV, most nearly full length, GAG region is heterogenous and POL and ENV are highly conserved. Not expressed and seem to lack fxal enhancer seq in LTR. Endogenous ENV is 99% same as B ENV so B thought to be A and endogenous recomb
c a mutation from A, not a recomb
FeLV tumourogenesis mechs
Only occur after long latent period
Latency maintainance linked to neutr Ab presence and B ENV seq may enhance persistance
Tumourogenesis can follow either transduction or inserinal mutagenesis
Dna virus interaction with host cell
Productive lytic infection
Non prod infection in which virus doesnt compelete growth cycle and can transform cell
(Virus needs dna which is only avaikable in cell cycle not G0, rna is available all the time)
Transforming pro of dna birus fx
Often multifxal and act ti drive the cell into cell cycle or stop apoptosis
Dna Viral interactions with cell pro
Proto oncogene act
Anti oncogene inact
Normally disrupt p53 and Rb fxs as tumour suppressor pros by blocking cell cycle at G1
Bovine papilloma virus
Prod papillomas - benign, gen regress normally, can occassionally become malignant due to a cocarcinogen eg UV light around eyes or bracken in alimentary tract
Alpha herpes virus mareks dis
Transform t lymphocytes cause prolif and prod lethal gen lymphomatosis
Contagious transmit by shesdding from feather follicles and is major issue for poultry industry
Vacc originally rom related turkey birus, now with attrnuated MDV - used to counter emergence of new pathogenic strains with increased neoplastic potential. These strains pose a serious threat ti future vacc control. Meq (a transcription regulator) is a main biral pro assoc with oncogen
Mareks dis pathogenesis
Inhale dander Epi cells in lungs Viraemia macro Lympho Prolif Lymphoblastoid cells (death or regress)
Gamma herpes virus EBV
Infects B cells induces burkitts lymphoma and nasopharyngeal carcinoma in hum
EBV genome has multiple copies in each transformed cell some integrated but most in cytoplasm freely replicating
Cells prod viral antigen but not intact virion
Malignant cells have chrom abnormality - translocation of distal part of chrom 8 containing c-myc (gene expr in cell cycle) gene to chrom 14 so c-myc now under Ig promoter control so expr is incr
