Papilloma virus Flashcards
1
Q
human papilloma virus characeteristics
A
- 40 types each associated with a specific site
- all replicate in stratified epithelium, skin or mucosa, coordination with epithelial differntiation
- HPV is the most common sexually transmitted disease in humans
- most cervical cancer is caused by 16 or 18
- recent vaccines promise to greatly reduce cervical cancer incidence
2
Q
HPV structure and genome
A
- ds circular DNA
- organized into chromatin using cell histones
3
Q
HPV entry and transport
A
- adsorption using basal cell specific receptors
- entry via endocytosis and fusion
- transport to nucleus
4
Q
hpv early transcription and translation
A
- early synthesis of E1 and E2 mRNA using cell specific promotoer and differential splicing. synthesis does not require viral activities
- synthesis of early proteins E1 and 2
- E2 is the master regulator of viral gene expression, it directs synth of other early mRNA’s including E6 and 7
5
Q
HPV DNA replication
A
- E1 and E2 recruit cell DNA replication machinery to HPV origin
- replicates like cellular DNA- RNA primers, leading and lagging strands, etc
6
Q
problem with using the cell machinery to make RNA and proteins
A
- most cells in the human body are not in an actively dividing state and the machinery that the virus needs in not active
- it needs to modify the host cells so that they continue to grow
- binds p53 in order to prevent cell death by apoptosis
- binds Rb and other proteins stimulating entry into the cell cycle
- direct initiation of DNA replication via E2
7
Q
HPV late gene expression
A
- keratinocytes differentiation activates late promoter and stimulates DNA replication
- differential splicing to give mRNAs for L1 and L2 capsid proteins
- transport of L1 and 2 proteins to nucleus for assembly into capsid
8
Q
hpv assembly
A
- assembly of capsids, stuffing with viral capsid
- release of virion as cells differeniate, die, and slough off
9
Q
HPV 16 and 18 in cervical epithelium, development of malignant cells
A
- the key event: very rare integration of part of viral genome into host DNA in a small fraction of infected cells
- selecation of cells containing integrated E6,7, but not E2
- continued synthesis of E6,7 proteins (no late events) drives cells into cycle and prevents apoptosis
- multiplication of a very small fraction of infected cells into a malignant tumor
10
Q
retroviruses
- examples
- diseases
- transmission
- replication (defining feature)
- inheritance
- fossil record
A
- HIV, HTLV, Foamy virus
- Cancers, AIDS
- transmitted by close contact: sexual, mother to offspring, blood
- replicate through a DNA intermediate (provirus) which integrates into the host genome
- can also integrate into the germiline DNA to become inherited endogenous provirus, which constitutes about 8% of our genome
- this provides a fossil record of retrovirus evolution going back tens of millions of years
11
Q
retrovirus structure and genome
A
- enveloped
- single stranded plus RNA
12
Q
retrovirus early events
A
- adsorption
- penetration
- synth of dsDNA
- integration into host DNA
13
Q
retrovirus DNA synthesis
A
- synth of minus DNA to 5’ end using a tRNA primer
- transfer of DNa to 3’ end with continued synthesis of minus strand
- completion of minus and plus strand DNA
- completion of synth with U3RU5 as long terminal repeat (LTR). transfer to nucleus
14
Q
retrovirus DNa integration
A
-integration into (more or less) random sites of cellular DNA
15
Q
retrovirus provirus expression
A
- transcription: promoter elements in LTR allow regulation
- splicing of env mRNA
- transfer to cytoplasm
16
Q
retrovirus late events
A
- viral protein synth (gag, pol on free ribosomes, env on ER)
- assembly of virions at cell surface
- release by budding, cleavage of gag, pol proteins
- cells usually survive and produce more viruses
- if oncogene is present then altered shape and growth properties are acquired
17
Q
retrovirus transformation
A
-in a rare infected cell, LTR can drive overexpression of a protooncogene
