Reproductive cycle of a papillomavirus in a host cell. A study of pdz protein expression during the human papillomavirus life cycle james, claire deborah 2015. Each papillomavirus type has specific epithelial sites where it can initiate a productive life cycle, as well as sites where virus entry occurs in the absence of lesion formation. In some instances, such as following hpv16 infection of the cervix or cottontail rabbit papillomavirus crpv infection of domestic rabbits, papillomaviruses can undergo abortive infections in which the productive cycle of the virus is not completed. The role of stat3 during the human papillomavirus hpv. A study of pdz protein expression during the human papillomavirus life cycle. Human papillomavirus infection hpv infection is an infection caused by the human papillomavirus hpv. After the entry in the cells, the virus requires the expression of e1 and. Transcription introduction at the time of writing, the papillomaviridae pv family of viruses is composed of over 450 distinct types of human papillomavirus hpv and over 200 animal papillomaviruses.
Biology and pathogenesis 5 the viral genome of the hpv consists of a single molecule of doublestranded and circular dna, containing approximately 8000 base pairs and harboring an average of 8 open reading. As the timing of life cycle events affects the accessibility of viral antigens to the immune. The fact that the papillomavirus life cycle strictly requires keratinocyte differentiation has posed a substantial barrier to the study of papillomaviruses in the laboratory, since it has precluded the use of conventional cell lines to grow the viruses. The family papillomaviridae is a group of small, nonenveloped viruses with doublestranded. Of the 100 or so types that have been identified, around 40 can infect the cervix, with a subset of these causing lesions that can progress to highgrade neoplasia and cervical cancer. Although their lifecycle organisation is broadly similar to that of the lowrisk hpv types, the two groups differ significantly in their capacity to drive cell cycle entry.
Papillomaviruses infect epithelial cells, and depend on epithelial differentiation for completion of their life cycle. Among the hpv associated cancers, cervical cancer still ranks. Pointer cottontail rabbit papillomavirus crpv model. It is not intended to be and should not be interpreted as medical advice or a diagnosis of any health or fitness problem, condition or disease. Immunology and vaccinepreventable diseases pink book. Hpv is the most common sexually transmitted infection sti.
Hpv dna testing in cervical screening, as well as the development of. We found that the ability of hpv16 to reprogram suprabasal cells to support dna synthesis correlates with e7s ability to bind pocket proteins but not its. The doublestranded, circular dna genomes of all hpvs are approximately 8 kb in size. Organotypic raft culture has had a dramatic impact on our understanding of the papillomavirus life cycle. The expression of viral gene products is closely regulated as the infected basal cell migrates towards the epithelial surface. Pdf human papillomavirus hpv is one of the most common causes of sexually. Human papilloma virus hpv infects basal keratinocytes of the stratified epithelium, and its life cycle is tightly linked to the normal differentiation. The hpv life cycle begins with infection of stem cells in the basal layer of the epithelium.
Papillomavirus life of cycle, cervical neoplasia hpv16 papilloma cervical cancer warts differentiating epithelium a b s t r a c t human papillomaviruses hpvs comprise a diverse group, and have different epithelial tropisms and life cycle strategies. A methods for introduction of viral genomes into keratinocytes vary 6,7,33,4 but the basic procedure involves the cotransfection of a circular. Pdf biology and natural history of human papillomavirus infection. Knowledge of the hpv infectious life cycle and hpvassociated cancer progression has. Life cycle organization during productive infection by hpv types from supergroup a. The family papillomaviridae is a group of small, nonenveloped viruses with double stranded. Papillomavirus types found in humans are divided into five genera based on dna sequence analysis, with the different types having different life cycle characteristics and disease associations.
The hpv life cycle begins with the infection of stem cells. Establishment of the human papillomavirus type 16 hpv16 life cycle in an immortalized human foreskin keratinocyte cell line. Disease markers 23 2007 2973 297 ios press papillomavirus life cycle organization and biomarker selection john doorbar national institute for medical research, the. The content on this site is presented in a summary fashion, and is intended to be used for educational and entertainment purposes only. Transcriptional regulation during the papillomavirus life cycle and elimination of infection using homologous recombination andrew robert carson, phd university of pittsburgh, 2006 human papillomaviruses hpvs require terminal differentiation of the host cell to produce infectious virions.
Human papilloma virus life cycle and carcinogenesis ncbi. Knowledge of the hpv infectious life cycle and hpvassociated cancer progression. Hpvs are nonenveloped viruses with icosahedral capsids that replicate their genomes within the nuclei of infected host cells. After infection in this case through a cut, the viral genome is. Human papillomavirus virions invade through damaged. The biology and lifecycle of human papillomaviruses ucla health. Pathogenesis of human papillomaviruses in differentiating. In virions, the hpv dna is found associated with cellular histones to form chromatinlike complexes. Human papillomaviruses hpvs target the stratified epidermis, and can causes diseases ranging from benign condylomas to malignant tumors. The hpv life cycle typically progresses with the circular viral genome maintained in the nucleus as an episome, or a genetic element separate from the host genome 36. Classification of papillomaviruses, taxonomy of human papillomaviruses, important definitions, life cycle and malignancy of hpv16, vaccines, bibliography, and more at metapathogen. The human papillomavirus hpv life cycle and the stroma. Human papillomaviruses hpv activate a number of host factors to control their differentiationdependent life cycles.
Productive papillomavirus life cycle and nonproductive infection. The life cycle of human papillomavirus springerlink. A diagrammatic representation of the skin to reveal the pattern of hpv16 gene expression as the infected cell migrates towards the epithelial surface. The relationship of cervical cancer and sexual behavior was suspected for more than 100 years and was established by epidemiologic studies in the 1960s. Productive lifecycle of human papillomaviruses that. Human papillomaviruses hpvs are a diverse group of viruses that cause epithelial lesions of varying severity. As with other dna tumour viruses, such abortive infections can predispose to cancer. Human papillomavirus hpv is a nonenveloped doublestranded dna virus that undergoes its life cycle in either the mucosal or the cutaneous stratified squamous epithelia 3. Most sexually active men and women being exposed to the virus at some point during their lifetime. John doorbar, division of virology, national institute for medical research, london, uk speaks on papillomavirus life cycle regulation in infected epithelium. Genital hpv infection cdc fact sheet human papillomavirus hpv is the most common sexually transmitted infection in the united states. Human papillomavirus is the most common sexually transmitted infection.
The natural history of human papillomavirus infections of. Cervical cancer is caused by human papillomavirus infection. Steinberg2 1department of biochemistry and molecular genetics, the university of alabama at birmingham, birmingham, al, usa. A new cell culture model to genetically dissect the. The natural history of human papillomavirus infections of the mucosal epithelia louise t. The virus exclusively infects epithelium and produces new viral particles only in fully mature. However, the requirement for immortalization restricts the study to only a few hpv types and does not allow investigating immediate early events of the viral life cycle.
This chapter provides an overview of the life cycle of the human papillomavirus hpv, including. Other supergroup a viruses, such as hpv2 and hpv11 follow a similar pattern. Papillomavirus life of cycle, cervical neoplasia hpv16 papilloma cervical cancer warts differentiating epithelium a b s t r a c t human papillomaviruses hpvs comprise a diverse group, and have different epithelial tropisms and. The individual isolates for papillomavirus are very speciesspecific. This phenomenon has also been described for human papillomavirus hpv vegetative genome replication, which. Because infectious bpv1 virions can be extracted from the large warts the virus induces on. Shown is the circular, 7900 base pair bp doublestranded dna dsdna genome of hpv18. Expression of e6 and e7 in the lower epithelial layers drives cells into sphase, which creates an environment that is conducive for viral genome. Papillomavirus research aims to publish top quality articles, describing innovative research advances in the field of human tumour virology, including epstein barr virus ebv, human t cell leukemia virus htlv, polyoma virus pyv, merkel cell polyomavirus mcpyv, kaposis sarcoma herpes virus kshv and papillomaviruses pv, as well as other related animal tumour virus models.
The human papillomavirus replication cycle, and its. Some health effects caused by hpv can be prevented by the hpv vaccines. Life cycle heterogeneity in animal models of human. Human papillomavirus and cervical cancer the lancet. The manipulation of these host cell signalling pathways can result in the developement of cancer and hpv is responsible for around 5% of all cancers worldwide. Viruses 2017, 9, 219 3 of 21 viruses 2017, 9, 219 3 of 20 figure 1. The cell cycle timing of human papillomavirus dna replication. Infections of hpvs in the genital tract are among the most common sexually transmitted diseases, and a major risk factor for cervical cancer.
Papillomavirus life cycle organization and biomarker selection. In recent years, it has become clear that many hpv types, including the majority of those contained within the beta and gamma genera, cause only asymptomatic infections in immunocompetent. Ubira etheses a study of pdz protein expression during. To cause a lesion andor to initiate a latent infection, the virus particles have to gain access to the epithelial basal cells at sufficiently high levels. About 90% of hpv infections cause no symptoms and resolve spontaneously within two years.
Entry of hpv into the basal cells of stratified epidermis. Productive lifecycle of human papillomaviruses that depends upon. Pointer cottontail rabbit papillomavirus crpv model system to test antiviral and immunotherapeutic strategies neil d christensen. The normal hpv life cycle is strictly epithelial 5 and several studies have shown that hpv dna is absent in the blood of women with cervical hpv infection, whereas it is detect able in patients.
Human papillomavirus hpv and cancer cancer education project university of rochester. Natural history biological perspective workshop title. Analyzing the human papillomavirus hpv life cycle in. The process of viral maturation involves a variety of. The biology and lifecycle of human papillomaviruses. Establishment of the human papillomavirus type 16 hpv16. These highrisk types are prevalent in the general population, and can predispose to the. Division of virology, national institute for medical research, the ridgeway, mill hill, london nw7 1aa, uk received 19 august 2004. Model systems of human papillomavirusassociated disease. Each papillomavirus type showed a distinctive gene expression pattern that could be explained in part by differences in tissue tropism, transmission route, and persistence. One strategy utilized by dna viruses is to replicate their genomes nonconcurrently with the host genome. Human papillomavirus hpv is the most common sexually transmitted infection in the united states. Author summary current cell culture models for the study of the human papillomavirus hpv life cycle depend on immortalized keratinocytes harboring episomal hpv genomes. All of these isolates are tropic for squamous epithelial cells but the.