# NUR CEREN KABAKCI - 1605A014 ***Human papillomavirus (HPV)***


Reference : Human Papillomaviruse
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 64
https://www.ncbi.nlm.nih.gov/books/NBK424408/

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# HPV
*HOST:*
* Human epithelial cells, dermal fibroblasts

*GENOME:*
* Double stranded DNA
* Circular - covalently closed
* 7500–8000 base pairs (bp) (about 4950–5280 kDa)

*VIRION:*
* Non-enveloped
* 55 nm in diameter

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Since papillomaviruses cannot be grown efficiently in tissue culture, studies on the architecture of the virus particles were originally restricted to those viruses that can be obtained from naturally occurring tumours, such as bovine papillomavirus (BPV), human papillomavirus type 1 (HPV-1) and cotton-tail rabbit papillomavirus (CRPV)

Virus-like particles of BPV-1, CRPV, HPV-1, -6, -11, -16, -18 and -33 can be obtained by expression of the structural proteins in recombinant vectors such as vaccinia or baculo-viruses

The major capsid protein, L1, appears to be sufficient for particle formation

The antigenic and structural properties of virus-like particles were shown to be similar to those of virions
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Phylogenetic tree of 95 human and animal papillomaviruses
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# FAMILY
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* ***Table:*** Some taxonomic association and origin of HPV types
* Taxonomic orders based on similarities in sequence of E6, E7 and L1 genes helped to identify groupings of related HPVs
* Five supergroups of papillomaviruses can be distinguished, of which three contain HPVs (supergroups A, B and E)
* 70 HPV types have been described in total
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Notable HPV types and associated diseases

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# Virion

**Figure:** SEM image of HPV

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## Genomic structure and properties of gene products
- The circular DNA genome of all papillomaviruses can be divided into three segments of unequal size.
- The long control region (LCR), also called the upstream regulatory region (URR) or non-coding region (NCR), represents about 10% of the genome.
- The early (E) and late (L) genes are coded by about 50 and 40% of the genome, respectively.
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* The papillomavirus genome can be divided into three regions:
* * The long control region contains cis-responsive elements, which are required for the regulation of gene expression and DNA replication.
* * The early region codes for proteins involved in the regulation of viral transcription (E2), viral DNA replication (E1 and E2), cell proliferation (E5, E6 and E7) and,
* * Possibly, some late steps in the viral life cycle (E4). The late region contains two genes, which code for the capsid proteins L1 and L2.
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# Regulation of gene expression

In principle, the mechanisms have to achieve the following:
(i) epithelial-specific transcription;
(ii) differential expression of papillomavirus genes during the differentiation of squamous epithelia, in particular the switch from early to late genes;
(iii) feedback control by papillomavirus gene products, which may play an important role in the persistence of papillomavirus infections;
(iv) response to physiological factors of the infected host on papillomavirus gene expression. Many or all of these phenomena are deregulated during malignant progression of papillomavirus lesions.
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**Figure:** Schematic representation of the HPV-16 LCR
* Four E2 binding sites, typical for the LCRs of all genital HPVs, serve as landmarks in its molecular organization. Counting from the 5′ side, the first and second E2 binding sites divide the LCR into three functionally distinct segments.

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# Replication Cycle
***Entry***

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***Infection (Early and Late Events)***

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***Full Cycle***

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There is sufficient evidence in humans for the carcinogenicity of human papillomavirus (HPV) types 16 and 18.

There is evidence suggesting lack of carcinogenicity to the cervix in humans of HPV types 6 and 11.

There is limited evidence in humans for the carcinogenicity of some other HPV types.

HPVs cannot infect animals. Some animal papillomaviruses cause cancer in their natural hosts.

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HPV types 16 and 18 are carcinogenic to humans (Group I).

HPV types 31 and 33 are probably carcinogenic to humans (Group 2A).

Some HPV types other than 16, 18, 31 and 33 are possibly carcinogenic to humans (Group 2B).

The carcinogenicity of HPV types 16 and 18 is supported by experimental evidence that proteins of these viruses interfere with the functions of cellular regulatory pathways.
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