expression of human papilloma virus E4 proteins in differentiating epithelia

by Anthony J. L. Hitch

Publisher: University of Birmingham in Birmingham

Written in English
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Thesis (Ph.D) - University of Birmingham, Institute for Cancer Studies, Faculty of Medicine and Dentistry, 1999.

Statementby Anthony J.L. Hitch.
ID Numbers
Open LibraryOL18449064M

  Early ORFs encode for E1, E2, E4, E5, E6 and E7 proteins. E1 and E2 proteins bind to viral origin of replication, recruit cellular proteins that mediate viral DNA replication, and regulate viral gene expression [3, 7].E1 and E2 are also responsible for the maintenance of viral DNA as an episome during initial HPV infection, and also during latent infection in the basal cell layer [3, 10, 34]. virus infectious cycle is rather complex and can explain the duration of an HPV infection. It involves both temporal and spatial separation of viral protein expression. The virus first infects a keratinocyte in the basal layer of the epithelium as a consequence of microtrauma, i.e., an abrasion of the epithelium that. The abundant human papillomavirus type II (HPV 11) [email protected]?E4,E5 transcript potentially encodes the [email protected]?E4,E5a and E5b proteins. It is not known if either of the E5 proteins . These two HPV proteins act in a cooperative fashion to promote cell proliferation so the virus can utilise the host’s DNA replication machinery, and to ensure cell survival such that the virus replicates before the cell dies. The E6 and E7 proteins of high-risk viruses have .

  Human Papillomavirus is the major etiological agent in the development of cervical cancer but not a sufficient cause. Despite significant research, the underlying mechanisms of progression from a low-grade squamous intraepithelial lesion to high grade squamous intraepithelial lesion are yet to be understood. Deregulation of viral gene expression and host genomic instability play a central role.   The E1 protein binds to the origin of replication ().The E2 ORF encodes protein that act as a transcriptional activator of HPV gene expression in both normal and immortalized keratinocytes (32,33).The E2 proteins bind to E1 and stimulate viral DNA replication ().The E4 is expressed as a late gene with a role in the productive infection. Human papillomavirus infection (HPV infection) is an infection caused by human papillomavirus (HPV), a DNA virus from the Papillomaviridae family. About 90% of HPV infections cause no symptoms and resolve spontaneously within two years. However, in some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase. RESULTS: Grouped together, the lesions of dysplasia (mild to severe) and squamous cell carcinoma were found to be 16 times more likely to express human papilloma virus E6 mRNA than the benign lesions (P); in the lesions of immunosuppressed patients, human papilloma virus 16 E6 was roughly 10 times more likely to be expressed than in.

Human papillomavirus-positive oropharyngeal cancer (HPV-positive OPC or HPV+OPC), is a cancer (squamous cell carcinoma) of the throat caused by the human papillomavirus type 16 virus (HPV16). In the past, cancer of the oropharynx (throat) was associated with the use of alcohol or tobacco or both, but the majority of cases are now associated with the HPV virus, acquired by having oral contact.   Author summary Oncogenic human papillomavirus (HPV) infection causes cancers of the anogenital and oropharyngeal tracts. HPV infects undifferentiated basal cells of the epithelium at these body sites and expresses low levels of viral early genes, required for replication of the viral genome. In normal epithelia, cellular migration away from the basal layer induces cell cycle exit and. protein expression. Following differentiation of the keratinocyte, early HPV genes are expressed and the viral episome is further amplified to higher copy numbers. Viral late protein expression and virus assembly occurs during terminal differentiation of the keratinocyte and viruses are shed from the outermost layer of epithelial cells. HPV. The L1 open reading frame is the most conserved region in the HPV genome and has, therefore, been used to define papillomavirus types. Distinct HPV types are characterized by greater than 10% dissimilarity to the closest known type within the L1 open reading frame (De Villiers et al. ).A great deal of sequence similarity also exists in the E1, E2, and L2 open reading frames, with somewhat.

expression of human papilloma virus E4 proteins in differentiating epithelia by Anthony J. L. Hitch Download PDF EPUB FB2

SUMMARY Human papillomaviruses (HPV) are the etiological agents of cervical and other anogenital malignancies. Over different types of HPVs have been identified to date, and all target epithelial tissues for infection.

One-third of HPV types specifically infect the genital tract, and a subset of these are the causative agents of anogenital by: REGULATION OF HUMAN PAPILLOMAVIRUS GENE EXPRESSION IN DIFFERENTIATING EPITHELIA Two major promoters direct the expression of HPV ORFs during the early and late phases of the viral life cycle.

Most HPV mRNAs are polycistronic, and many carry three or more ORFs. Expression of various early genes is regulated, in part, by alternative splicing Cited by:   An abundant human papillomavirus (HPV) protein E1^E4 expression of human papilloma virus E4 proteins in differentiating epithelia book expressed late in the virus life cycle in the terminally differentiated layers of epithelia.

The expression of E1^E4 usually coincides with the onset of viral DNA amplification. However, the function of E1^E4 in viral life cycle is not completely by: The six early proteins; E1/E2: protein that control the function of E6 and E7 genes, E4: protein function basically unknown but may control virus release from host cell, E5: hydrophobic protein.

Grussendorf, E. I., and zur Hausen, H.,Localization of viral DNA replication in sections of human warts by nucleic acid hybridization with complementary RNA of human papilloma virus type 1, Arch.

Dermatol. Res. 55– PubMed CrossRef Google ScholarCited by:   This study provides a first characterisation of β-HPV life-cycle events in tumours abscised from EV patients (the human model of β-HPV-induced skin cancer), and shows how changes in E4 expression patterns relate to disease severity.

β-HPV life-cycle has also been reconstructed in organotypic raft cultures created using EV-derived keratinocytes. The HPV replication cycle is tightly linked to host cell differentiation. The virus displays a tightly orchestrated gene expression program that results in epithelium stratum-specific production of viral proteins (Doorbar, ).The HPV genome can be categorized into three parts: the long control region (LCR), the early region and the late region (Fig.

1A). In the tissue culture, the transforming properties of HPVE6 anf E7 gene encode proteins are more stronger than HPV E5. In human cancer E6 and E7 are normally found to be expressed. Indeed, in many HPV-associated cancers, integration of the viral genome into the host genome leads to the selective retention of intact E6 and E7 genes, which.

Human papillomaviruses Figure HPV DNA crude prevalence and HR-HPV type-specific prevalence among women with normal cytology by world region: meta-analysis including women from 36 countries ‘Other HR’ includes the 6 most common HPV types in cervical cancer other than 16 and HPV, 33, 35, 45, 52, Two major human papillomavirus type 1 (HPV-1) E4 proteins are found in large amounts in productively infected differentiating wart cells, a kDa protein translated from an E1-E4.

To test this, we constructed AdE1 − vectors expressing the human papilloma virus 16 (HPV) proteins E6 and E7. Expression of both E6 and E7 from these vectors partially complemented adenoviral DNA replication activity in vitro, in SK-Hep1 cells and primary human astrocytes, as well as in vivo in mouse liver.

The human papillomavirus type 16 E5 protein (HPV16 E5) down-regulates surface expression of HLA-I molecules. The molecular mechanisms underlying this effect are so far unknown. An abundant human papillomavirus (HPV) protein E1/\E4 is expressed late in the virus life cycle in the terminally differentiated layers of epithelia.

The expression of E1/\E4 usually coincides with the onset of viral DNA amplification. However, the function of E1/\E4 in viral life cycle is not completely understood. Viral proteins. The early HPV ORFs include E1, E2, E4, E5, E6, E7 and E8, (see Fig.

1).E1 codes for an ATP dependent viral DNA helicase that can bind to the AT-rich origin of replication and E2 proteins function in viral transcription, replication and genome partitioning. The full length E2 protein encodes a transcriptional activator.

The expression system used provides fusions to the N‐terminal part of the MS2 polymerase gene controlled by the heat‐inducible lambda PL promoter. Using the purified fusion proteins as immunogens we raised antisera against the proteins encoded by the ORF E6, E7 and E1 of HPV 18 as well as those encoded by the ORF E6, E7, E4 and L1 of HPV Antibodies prepared against a human papilloma virus-1 (HPV-1) E4/beta-galactosidase fusion protein identified several polypeptides in HPV-1, but not HPV-2 or 4, induced papillomas.

The major E4 protein, that represented up to 30% of total cellular protein, was a 16/K doublet which was purified by column chromatography and analysed for amino. The most highly expressed protein during the productive phase of the human papillomavirus (HPV) life cycle is E1^E4.

Its full role during infection remains to be established. HPV E1^E4 is expressed during both the early and late stages of the virus life cycle and contributes to viral genome amplification. In an attempt to further outline the functions of E1^E4, and determine whether it plays a.

Human papillomavirus major capsid protein (HPV L1) is the main protein constituent of the HPV particle coat. The HPV particle coat is highly immunogenic and it can effectively stimulate the humoral immunity and cellular immunity of human body, thus preventing the body from being re-infected by the same HPV [1, 2, 3, 4].This is the main reason why the L1 protein is used as HPV prophylactic.

Vaccinia virus vectors were used to express the major (L1) and minor (L2) capsid proteins of human papillomavirus type 1 (HPV-1) with the vaccinia virus early (pK) or late (pSynth, p11K) promoters. Human Papillomavirus Type 16 E6 and E7 Proteins Inhibit Differentiation-dependent Expression of Transforming Growth Factor-b2in Cervical Keratinocytes Matthias Nees, Joel M.

Geoghegan, Peter Munson, Vinayakumar Prabhu, Yun Liu, Elliot Androphy, and Craig D. Woodworth 1. Structure of viral particle and regulation of gene expression The human papillomavirus (HPV) is a relatively small non-enveloped virus that contains a double-stranded closed circular DNA genome, associated with histone-like proteins and protected by a capsid formed by two late proteins, L1 and L2.

Each capsid is composed of Human papillomaviruses (HPV) are the etiological agents of cervical and other anogenital malignancies. Fingerprint Dive into the research topics of 'Pathogenesis of human papillomaviruses in differentiating epithelia'. Together they form a unique fingerprint.

The functions of the E5 and E1 E4 proteins are still largely unknown, but. HPV16 (human papillomavirus type 16) is a kb double-stranded DNA virus that infects anogenital mucosal epithelia.

In some rare cases, in women, infection can progress to cervical cancer. Human papillomavirus gene expression. to correct spatial and temporal expression of the various virus proteins within the infected epithelium.

high-risk human papillomaviruses in a. Fifteen strains of Papillomaviridae are known to cause cervical cancer. HPV is considered a high-risk HPV type as the risk of cancer may be higher than for other high-risk HPV types. The two virally encoded proteins of HPV are L1 and L2.

L1 is the main capsid protein that forms the outer shell of the virus. Human papillomavirus type 1 (HPV1) E4 protein is associated with cytoplasmic and nuclear inclusions in productively infected keratinocytes.

Here we have used transient expression of HPV1 E4 (also known as E1^E4) protein in keratinocytes to reproduce formation of E4 inclusions. The human papillomavirus (HPV) E6 and E7 proteins have been the most frequently characterized with respect to their effects on cellular proliferation and, to some degree, on differentiation.

Some of the pro-proliferative mechanisms employed by HPV E6 and E7 are shared by other DNA tumor viruses that do not specifically infect stratified epithelia.

T1 - Human papillomaviruses target differentiating epithelia for virion production and malignant conversion. AU - Laimins, Laimonis A.

PY - /1/1. Y1 - /1/1. N2 - Human papillomaviruses infect stratified epithelial cells and induce hyperproliferative lesions. Human papillomavirus (HPV) is a small, non-enveloped deoxyribonucleic acid (DNA) virus that infects skin or mucosal cells.

The circular, double-stranded viral genome is approximately 8-kb in length. The genome encodes for 6 early proteins responsible for virus replication and 2 late proteins, L1 and L2, which are the viral structural proteins. Human papillomavirus major capsid protein (HPV L1) is the main protein constituent of the HPV particle coat.

The HPV particle coat is highly immunogenic and it can effectively stimulate the humoral immunity and cellular immunity of human body, thus preventing the body from being re-infected by the same HPV [1–4].This is the main reason why the L1 protein is used as HPV prophylactic.

The natural history of human papillomavirus infections of the mucosal epithelia LOUISE T. CHOW,1 THOMAS R. BROKER1 and BETTIE M. STEINBERG2 1Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA; and 2The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System.Figure 2.

Early gene expression profile of human papillomavirus type 16 in W12 cervical epithelial cells. Open boxes represent open reading frames, with the proteins encoded indicated by bold text.E4.

Although E4 proteins are expressed at low levels during the early phase of viral infection, expression of E4 increases dramatically during the late phase of infection. In other words, its "E" appellation may be something of a misnomer. In the case of HPV-1, E4 can account for up to 30% of the total protein at the surface of a wart.