HPV introduction Flashcards
What is the most common viral sexually transmitted infection
HPv
How many HPV infections are with a high-risk type linked to cancer
Half
Where is most HPV-associated disease (geographically)
LICs and MICs
What cell line contains HPV genes?
HeLa
In the 1980s what virus was mistakenly blamed for causing cervical cancer
HSV
Length of HPV genome
8kb
Shape of HPV genome
Circular
Is PV difficult to grow in culture cells
Yes
What skin ailment does HPV cause (skin and genital)
Papilloma
Condyloma
What type of HPV causes most HPV driven cancers, what’s runner up
HPV16, HPV18
What nucleic acid makes up the HCV genome?
dsDNA
How many strands of DNA are in HPV, also where are the ORFs
1 strand containing all the ORFs
How many ORFs in HPV
10
What are HPV ORFs classified into what two groups and on what basis?
Early or late, based on location in genome
What cells are early ORFs expressed
Non-productively infected cells –> reg. proteins and those required for replications
Late ORFs are only expressed in what type of cell
Capsid proteins, productively infected cells
LCR/URR meaning
Long control region / upstream regulatory region
What does the LCR/UUR contain
Ori of DNA replication, transcription factor control elements
E1 protein function
Initation of DNA replication (helicase)
E2 protein function
Transcription regulation/DNA replication
E3 protein function
Ubiquitin ligase
E4(E1^E4) function
Late early protein implicated in virus assembly/release
Function of E5
Oncoprotein and genome replication
Function of proteins E6 and E7
Oncoproteins and cell cycle modulation
E8 (E8^E2C) function
Potentially controls HPV replication levels
L1 function
Major capsid protein
L2 function
Minor capsid protein
HPV life cycle is dependent on what cell type differentiation
Keratinocyte
Genome maintence occurs in what epidermal layer, which HPV proteins
Basal layer, E1, E2
Genome maintance/cell proliferation occurs in what epidermal layer, what HPV proteins
Spinous, E1,5,6,7 and E8^E2
Genome amplification occurs in what epidermal layers and what HPV proteins
Top of spinous, mostly granular: E1,E2,E4,E6,E7
Virus assembly occurs at what epidermal layer, what proteins of HPV
Granular: L1,L2
Virion release of HPV occurs at what epidermal layers
Cornified
How does HPV enter the cell
Bind to receptor
Conformational changes of L1/L2 lead to cleavage by proteases like Furin
Endocytosis
What can enter through microtears in the epithelial
HPV
Where does disassembly of capsid and exposure of the geneome occur within the cell?
Endosome
Where does HPV hide in the cell
Golgi, needs cell division to enter nucleus
What pathway does HPV hide from and wait till it switches off?
cGAS
L2 utilised what complex to traffic genome into cytoplasm, enter nucleus and colocalise at ND10 bodies
Retromer
Transcription of HPV occurs in how many waves
2
P97 is what type of promotor and leads to direct expression of what
Early promotor in undifferentiated cells: E6 and E7
The late promotor is called ____, drives xcpression of what proteins in what type of cells
P670, immortalised differentiated cell: Proteins E4/L1/L2 and E1
The LCR contained enhancer elements are responsive to ___ as well as virus encoded _____________
AP-1. Virus encoded transcriptional regulatory factors
What do LCR elements bind to for example
E2
LCR is important in what part of the lifecycle
Latency
MAPKs are activated by what HPV proteins
E5, E6, E7
E2 proteins regulate what processes
Viral transcription, viral DNA replication and long term episome maintence
E2 proteins contain what domains and binding sites for what
Sequence specific DNA binding, dimerisation domain, transactivating domain (amino term)
Truncated E2 (lacking TA) can act as a repressor of what
Transcription
E2 can express to what promotor to regulate expression of what
P97, regulate E6 and E7
Why is negative transcription of proteins needed for HPV
So not too many oncoproteins are produced
Why does HPV replicate only in skin cells
Due to high DNA replication rate
Virals genomes replicate how often per cell cycle
Once
PV requires DNA ori in trans/cis and viral E1 and E2 proteins in trans/cis
PV requires DNA Ori in cis and viral E1 and E2 proteins in trans.
Minimial Ori requires what
AT rich region and E1 and E2 binding site.
E1 is what type of protein
Nuclear phosphoprotein, functions as ATP-dependent helicase
What does E2 stabilise
E1-Ori interaction
E1 brings cellular machinery like what
DNA polymerase, histone H1, cyclin E and UBc9
Efficient cell cycle regulated replication of PV depends on association of what
E1 and the S-phase specific cyclin E complex/
What occurs excuslively in differentiated keratinocytes
Vegetative DNA synthesis, capsid protein synthesis and virion assembly
Warts contain abundant ____ protein transcripts
E4
Efficient escape requires what protein
E4
