ICL 1.12: Parvo, Papova & Poxviruses Flashcards
what type of virus are parvoviruses?
naked DNA virus
what type of viruses are polyomaviruses?
naked DNA virus
what type of viruses are papillomaviruses?
naked DNA viruses
what type of viruses are poxviruses?
enveloped DNA viruses
which viruses are associated with cancers?
- papillomaviridae
- herpesviridae
- hepadnaviridae
- retroviridae
- flaviviridae
the cancers are usually cancers of the cells that the virus infects; it’s because the virus is changing the cell programing to keep them dividing
also the viruses are usually very specific for a certain type of cancer
which cancers are associated with the papillomaviridae family?
virus: human papillomaviruses
benign disease: benign warts
tumor: cervix, skin, anus, penis
which cancers are associated with the herpesviridae family?
#1 virus: EBV
benign disease: infectious mononucleosis
tumor: Burkitt’s lymphoma, Hodgkin’s lymphoma, B lymphoproliferative disease and nasopharyngeal carcinoma
#2: virus: Kaposi's sarcoma-associated herpesviruses
benign disease: Castleman’s disease
tumor: Kaposi’s sarcoma, body cavity lymphoma
which cancers are associated with the hepadnaviridae family?
virus: HepB
benign disease: hapatitis, cirrhosis
tumor: hepatocellular cancer
which cancers are associated with the retroviridae family?
virus: human T-lymphotropic virus 1
benign disease: tropical spastic paraparesis
tumor: adult T cell lymphoma
which cancers are associated with the flaviviridae family?
virus: HepC
benign disease; hepatitis, cirrhosis
tumor: hepatocellular cancer, lymphoma
what are papovaviruses?
polyomaviridae and papillomaviridae were formally called papovaviruses
what is SV40?
polyomavirus
SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans
like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors in animals, but most often persists as a latent infection
why is SV40 historically important?
SV40 is a polyomavirus that was the first DNA tumor virus isolated
studying it led to the concept of tumor antigens (T-Ag), oncogenes acting on cell p53 & RB to induce cells to divide, the nature of first eukaryotic promoter, splicing, first vector for introducing genes into cells, etc.
what are the general characteristics of the polyomavirus?
naked, icosahedral virion
very small genome
*circular dsDNA
how does the polyomavirus replicate?
this is a small circular dsDNA virus so there will only be E and L genes, no IE genes
the virus needs to get to mRNA so they will have highly active promoters that are recognized by transcription factors in the host
host RNA polymerase will transcribe a long primary transcript from the E region which is spliced into 2 mRNA – there are 2 possible splicing sites
the first splicing site creates a longer mRNA which leads to translation of a larger protein called large T antigen (T-Ag)
then the alternative splice site doesn’t remove a premature stop sequence so when you splice here, you get a smaller protein called small T antigen (t-Ag)
T-Ag and t-Ag are viral proteins that are very good at transforming cells to inactivate tumor suppressor genes so that the host cell will keep replicating
what does p53 do?
- it is a tumor suppressor that is mutated or abnormally expressed in many human cancers
- it allows cells to repair DNA damage or die by apoptosis
- it binds to DNA and activates or represses many genes
how do T-Ag and t-Ag interact with p53?
they are E genes products expressed in the polyomavirus!
T-Ag and t-ag from SV40 polyomavirus are precipated out and interact with p53 in the host cell
these viral proteins bind to the host p53 protein and inactivates it so that the virus can better replicate in the cell
what does T-ag do?
it’s an E gene product of polyomavirus that:
- induce cells to proliferate if they are in G0
- forms complexes with largest subunit of DNA polymerase a, p53 tumor suppressor protein, and p105RB + RB-related proteins
- turns on viral DNA synthesis
- binds to ori (origin of replication)
- turns on transcription of late genes turns off transcription of early genes
what does t-Ag do?
small t-Ag works with the large T-Ag in transformation of cells. Its targets are different: t-Ag binds a cell protein phosphatase and can activate pol II and pol III transcription
what are the two main human polyomaviruses?
- JC virus
- BK virus
70-80% of adults have antibodies to BK and JC viruses!! so most people have actually been exposed to this virus but only in immuno-compromised patients will it cause a problem
primary infection is in childhood
what is JC virus?
a polyomavirus = small naked virus with circular dsDNA
JC = John Cunningham virus
the hallmark of this virus is that it causes progressive multifocal leukoencephalopathy (PML)
PML is a demyelating disease so it kill oligodendrocytes that produce myelin for the CNS and it’s progressive so patients who get it will die within a few months
PML patients will have non-enhancing multifocal brain lesions in white matter that can be seen in brain imaging
only effects people where CD4+ < 200 like in HIV patients
what is BK virus?
a polyomavirus = small naked virus with circular dsDNA
BK causes nephropathy and other urinary tract problems like hemorrhagic cystitis –> this usually happens in kidney and BM transplant patients
mild respiratory illness common in renal transplant patients too
what are the clinical features of polyomaviruses?
polyomaviruses produce inapparent infections in natural hosts but are oncogenic in species different from their natural host
currently, polyomavirus-associated nephropathy (PVAN) is a serious, emerging complication in renal transplant recipients
how do you diagnose polyomaviruses?
PCR for genome DNA and ELISA for antibodies