Virology: Papillomaviruses and Polymaviruses Flashcards
oma means what?
tumour
Is inducing a tumour part of their normal lifecycle?
- nope it is a byproduct
Why are papillomaviruses and polyomaviruses of interest to us??
- common infection in humans - most of the time they rep fine and no harm to us
- cause life threatening human disease
L> Oncogenic: papillomaviruses cause anogenital, orpharyngeal and skin cancers …610,000 cancers in 2008, merkel cell polyomavirus is associated with skin cancer (common in men and extremely aggressive).
L> Immunosuppression: organ transplant and HIV infection = higher incidence with the viruses and cancer. - Powerful biological tools: allow us to study mechanisms of cancer , led to the discovery of p53 TS, aids in understanding DNA replication
Explain viral DNA replication wrt their small double stranded circular genome.
-small double stranded circular genome meaning they have a limited coding capacity (hence why they coevolved with humans to compensate), replicate in the nucleus and during normal virus life cycle the viral genome DOES NOT integrate into host DNA -> it stays inside the nucleus as its own separate circular DNA.
Explain viral DNA replication with respect to their replication system.
- do not encode an entire replication system
- one viral replication protein
- dependent on host cell for provision of replication factors eg DNA Poly
- encode viral proteins that orchestrate the host to induce replication factors and cell cycle regulators
Papillomavirus and polyomavirus genes contain what?
- infrons aka RNA SPLICING
- RNA splicing allows them to increase their coding capacity
- alt splicing allows the virus to make more different proteins vs what it could with its tiny coding capacity.
Describe the classification of papillomaviruses and polyomaviruses in terms of genome.
- DNA viruses
- Double stranded
- Non-enveloped
- Circular genome
aka small circular double stranded DNA viruses.
Viral gene expression (SV40 Replication):
- The genome is divided into what three functional domains. Explain them as well.
- Early: genes expressed early in virus infection (before viral DNA synthesis), continues to be expressed in late phase.
- Late: genes expressed late in infection cycle (during or after viral DNA synthesis)
- Non-coding: origin of viral DNA replication, regulatory motifs for polymerases and transcription factors to bind to
* *early and late genes expressed at different times in the life cycle.
Viral gene expression (SV40 Replication):
- Explain the function of early genes (non structural)
- they affect the host cell and virus functions :
- stimulate cell growth
- block cell death
- interact with viral origin of replication - initiation of viral DNA synthesis
- activate late viral gene transcription
Viral gene expression (SV40 Replication):
- Explain the f(x) of late genes (structural)y and egress
- late proteins are important for virion assembly.
- capsid proteins
- encapsidation of viral DNA into new virion
- egress of virus from the cell
HPV replicates in what tissue?
- epithelial tissue (stratified squamous epithelial more specifically)
- infection occurs in the basal as it moves up to be shed out. The host cell does not express any of the proteins needed for the viral replication therefore the virus needs to push host back into cell cycle.
Explain how HPV early proteins orchestrate the host cell.
- E7 stimulates cells to proliferate…the host cells natural response to this would be to induce apoptosis BUT
- E6 stops the host cell from dying…Rb = tumour suppressor protein wich controls when cells proliferate aka check point. E7 overcomes this.
- E6 targets P53 (this controls cells genome integrity ) = NO CELL DEATH YAY- NOT REALLY YA THOUGH.
- these in combination promote virus replication and survival of infected cells.
Explain how Polyomavirus early proteins orchestrate the host cell.
- early protein = large T antigen, LT which deregulates RB and p53 pathways as well therefore it has similar action in comparison to HPV.
