Papillomaviruses Flashcards
genome type
dsDNA
capsid structure
icosahedral
envelope?
naked
Does it require a packaged polymerase? why?
no because it replicates in the nucleus
What causes the “beads on a string” phenotype
host histones
Be familiar with the virus life cycle of papillomaviruses. You will not need to write this out from memory
a. L1 binds HSPGs
b. Conformational change in L1 exposes L2 which binds a tetraspanin-enriched region
c. Endocytosis
d. Acidification = uncoating
e. L2/vDNA go to golgi then nucleus
f. Transcription of early genes in nucleus
g. E2 tethers vDNA to host chromosomes so it replicates with host DNA
VAP
L1 protein
host receptor
L1 binds host HSPGs
Where specifically in the skin does the virus have to be introduced to establish infection?
Must be introduced to the basolateral membrane
Where does HPV replicate?
the nucleus because it tethers itself to the host chromosome
Understand the temporal gene expression as basal epithelial cells divide and differentiate to cornified epithelium. What sorts of genes are expressed in the initial stages of infection? In later infection, what is expressed? Why?
Initial = E(arly) genes
i. Cause aberrant proliferation, inhibition of apoptosis, immortalization
Later = L(ate) genes
i. Capsid proteins
ii. Don’t need structural proteins until you’ve reached the surface and can assemble and be released
Understand why HPV DNA replication is so slow in basal epithelial cells, but is amplified in differentiated, non-dividing cells.
a. Viral replication is caused by cell replication
b. Virus amplifies itself as the cell stops dividing because it knows it is nearing the surface
c. Allows stealth
Be familiar with the effects of HPV on cell transformation. Appreciate that transformation is required for successful infection, but does not necessarily lead to cancer.
E genes cause aberrant proliferation, inhibition of apoptosis, and immortalization
HPV can be acute, or remain for decades. Why is this the case? What determine if the virus is cleared or not?
a. Stealthy virus
b. Immune system has to recognize there is an infection
c. CD8+ T cells kills
d. Can have antibodies that prevent L1 from interacting with HSPG on basolateral membrane = no conformational change = no entry
Be familiar with the rationale of HPV recombinant vaccines and how they protect against HPV-associated cancers.
a. L1 protein self assembles into VLPs (empty shell)
b. Helps body create antibody response
