scholarly journals Characterization of Transcription Factor Binding to Human Papillomavirus Type 16 DNA during Cellular Differentiation

2006 ◽  
Vol 80 (9) ◽  
pp. 4356-4362 ◽  
Author(s):  
Andrew Carson ◽  
Saleem A. Khan
Keyword(s):  
Transcription Factors ◽  
Host Cell ◽  
Human Papillomaviruses ◽  
Host Protein ◽  
Regulatory Sequences ◽  
Regulatory Regions ◽  
Hpv 16 ◽  
Viral Genes ◽  
Cellular Transcription

ABSTRACT Human papillomaviruses (HPVs) require terminal differentiation of the host cell to produce infectious virions. The process of viral maturation involves a variety of changes in the expression/activity of host proteins that lead to high-level replication of the viral genome and expression of the late viral genes. Although the late promoter regions of HPV type 16 (HPV-16) are still not fully characterized, differentiation-dependent regulation of viral genes is thought to involve changes in the binding of host cell transcription factors to the viral promoter and regulatory regions. Currently, very little is known about specific cellular transcription factors involved in this process. We used the Panomics TransSignal protein/DNA array to identify changes in the levels of cellular transcription factors during methylcellulose-induced differentiation of W12 (20863) cells containing HPV-16. We then identified the differentially expressed transcription factors that specifically bind to HPV-16 DNA, including the known promoter and regulatory regions. We have validated the results obtained from the Panomics array by Western blot analysis. Furthermore, by chromatin immunoprecipitation assays, we have shown that many of the transcription factors identified in the above screen bind to the HPV-16 promoter/regulatory sequences in vivo and that the level of this binding is increased during differentiation. This approach identified approximately 30 transcription factors that specifically bind to HPV-16 sequences and may be involved in regulating HPV-16 transcription during differentiation. Although some of these transcription factors have previously been suggested to be involved in HPV-16 transcription, a number of them represent novel viral DNA-host protein interactions.

scholarly journals Identification of Two Cross-Neutralizing Linear Epitopes within the L1 Major Capsid Protein of Human Papillomaviruses

2002 ◽  
Vol 76 (13) ◽  
pp. 6480-6486 ◽  
Author(s):  
Alba-Lucia Combita ◽  
Antoine Touzé ◽  
Latifa Bousarghin ◽  
Neil D. Christensen ◽  
Pierre Coursaget
Keyword(s):  
Neutralizing Antibodies ◽  
Polyclonal Antibodies ◽  
Human Papillomaviruses ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Linear Epitopes ◽  
Cross Neutralization ◽  
Definition Of ◽  
L1 Protein

ABSTRACT The neutralizing activities of polyclonal antibodies and monoclonal antibodies (MAbs) obtained by immunization of mice with L1 virus-like particles (VLPs) were investigated by using pseudovirion infectivity assays for human papillomavirus type 16 (HPV-16), HPV-31, HPV-33, HPV-45, HPV-58, and HPV-59 to obtain a better definition of cross-neutralization between high-risk HPVs. In this study, we confirmed and extended previous studies indicating that most genital HPV genotypes represent separate serotypes, and the results suggest that the classification of serotypes is similar to that of genotypes. In addition, three cross-neutralizing MAbs were identified (HPV-16.J4, HPV-16.I23, and HPV-33.E12). MAb HPV-16.J4 recognized a conserved linear epitope located within the FG loop of the L1 protein, and HPV-16.I23 recognized another located within the DE loop. The results suggested that reactivity of MAb HPV-16.I23 to L1 protein is lost when leucine 152 of the HPV-16 L1 protein is replaced by phenylalanine. This confirmed the existence of linear epitopes within the L1 protein that induce neutralizing antibodies, and this is the first evidence that such linear epitopes induce cross-neutralization. However, the cross-neutralization induced by L1 VLPs represents less than 1% of the neutralizing activity induced by the dominant conformational epitopes, and it is questionable whether this is sufficient to offer cross-protection in vivo.

Influenza A viruses balance ER stress with host protein synthesis shutoff

2021 ◽  
Vol 118 (36) ◽  
pp. e2024681118
Author(s):  
Beryl Mazel-Sanchez ◽  
Justyna Iwaszkiewicz ◽  
Joao P. P. Bonifacio ◽  
Filo Silva ◽  
Chengyue Niu ◽  
...  
Keyword(s):  
Viral Replication ◽  
Er Stress ◽  
Host Cell ◽  
Messenger Rna ◽  
Influenza A ◽  
Nonstructural Protein ◽  
Host Protein ◽  
Stress Induction ◽  
Nonstructural Protein 1

Excessive production of viral glycoproteins during infections poses a tremendous stress potential on the endoplasmic reticulum (ER) protein folding machinery of the host cell. The host cell balances this by providing more ER resident chaperones and reducing translation. For viruses, this unfolded protein response (UPR) offers the potential to fold more glycoproteins. We postulated that viruses could have developed means to limit the inevitable ER stress to a beneficial level for viral replication. Using a relevant human pathogen, influenza A virus (IAV), we first established the determinant for ER stress and UPR induction during infection. In contrast to a panel of previous reports, we identified neuraminidase to be the determinant for ER stress induction, and not hemagglutinin. IAV relieves ER stress by expression of its nonstructural protein 1 (NS1). NS1 interferes with the host messenger RNA processing factor CPSF30 and suppresses ER stress response factors, such as XBP1. In vivo viral replication is increased when NS1 antagonizes ER stress induction. Our results reveal how IAV optimizes glycoprotein expression by balancing folding capacity.

scholarly journals Discovery of Transcription Factors and Regulatory Regions Driving In Vivo Tumor Development by ATAC-seq and FAIRE-seq Open Chromatin Profiling

PLoS Genetics ◽  
2015 ◽  
Vol 11 (2) ◽  
pp. e1004994 ◽  
Author(s):  
Kristofer Davie ◽  
Jelle Jacobs ◽  
Mardelle Atkins ◽  
Delphine Potier ◽  
Valerie Christiaens ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Tumor Development ◽  
Open Chromatin ◽  
Regulatory Regions ◽  
Chromatin Profiling

scholarly journals Targeting of the Visna Virus Tat Protein to AP-1 Sites: Interactions with the bZIP Domains of Fos and Jun In Vitro and In Vivo

1999 ◽  
Vol 73 (1) ◽  
pp. 37-45 ◽  
Author(s):  
B. A. Morse ◽  
L. M. Carruth ◽  
J. E. Clements
Keyword(s):  
Transcription Factors ◽  
Protein Interactions ◽  
Tat Protein ◽  
Protein Protein Interactions ◽  
Viral Promoter ◽  
Visna Virus ◽  
Cellular Transcription ◽  
Virus Promoter

ABSTRACT The visna virus Tat protein is required for efficient viral transcription from the visna virus long terminal repeat (LTR). AP-1 sites within the visna virus LTR, which can be bound by the cellular transcription factors Fos and Jun, are also necessary for Tat-mediated transcriptional activation. A potential mechanism by which the visna virus Tat protein could target the viral promoter is by protein-protein interactions with Fos and/or Jun bound to AP-1 sites in the visna virus LTR. Once targeted to the visna virus promoter, the Tat protein could then interact with basal transcription factors to activate transcription. To examine protein-protein interactions with cellular proteins at the visna virus promoter, we used an in vitro protein affinity chromatography assay and electrophoretic mobility shift assay, in addition to an in vivo two-hybrid assay, to show that the visna virus Tat protein specifically interacts with the cellular transcription factors Fos and Jun and the basal transcription factor TBP (TATA binding protein). The Tat domain responsible for interactions with Fos and Jun was localized to an alpha-helical domain within amino acids 34 to 69 of the protein. The TBP binding domain was localized to amino acids 1 to 38 of Tat, a region previously described by our laboratory as the visna virus Tat activation domain. The bZIP domains of Fos and Jun were found to be important for the interactions with Tat. Mutations within the basic domains of Fos and Jun abrogated binding to Tat in the in vitro assays. The visna virus Tat protein was also able to interact with covalently cross-linked Fos and Jun dimers. Thus, the visna virus Tat protein appears to target AP-1 sites in the viral promoter in a mechanism similar to the interaction of human T-cell leukemia virus type 1 Tax with the cellular transcription factor CREB, by binding the basic domains of an intact bZIP dimer. The association between Tat, Fos, and Jun would position Tat proximal to the viral TATA box, where the visna virus Tat activation domain could contact TBP to activate viral transcription.

scholarly journals Characterization of an E1A-CBP Interaction Defines a Novel Transcriptional Adapter Motif (TRAM) in CBP/p300

1999 ◽  
Vol 73 (5) ◽  
pp. 3574-3581 ◽  
Author(s):  
Mark J. O’Connor ◽  
Holger Zimmermann ◽  
Søren Nielsen ◽  
Hans-Ulrich Bernard ◽  
Tony Kouzarides
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Transcriptional Activation ◽  
Molecular Model ◽  
P53 Protein ◽  
Small Region ◽  
Adenovirus E1a ◽  
Cellular Transcription

ABSTRACT The adenovirus E1A protein subverts cellular processes to induce mitotic activity in quiescent cells. Important targets of E1A include members of the transcriptional adapter family containing CBP/p300. Competition for CBP/p300 binding by various cellular transcription factors has been suggested as a means of integrating different signalling pathways and may also represent a potential mechanism by which E1A manipulates cell fate. Here we describe the characterization of the interaction between E1A and the C/H3 region of CBP. We define a novel conserved 12-residue transcriptional adapter motif (TRAM) within CBP/p300 that represents the binding site for both E1A and numerous cellular transcription factors. We also identify a sequence (FPESLIL) within adenovirus E1A that is required to bind the CBP TRAM. Furthermore, an E1A peptide containing the FPESLIL sequence is capable of preventing the interaction between CBP and TRAM-binding transcription factors, such as p53, E2F, and TFIIB, thus providing a molecular model for E1A action. As an in vivo demonstration of this model, we used a small region of CBP containing a functional TRAM that can bind to the p53 protein. The CBP TRAM binds p53 sequences targeted by the cellular regulator MDM2, and we demonstrate that an MDM2-p53 interaction can be disrupted by the CBP TRAM, leading to stabilization of cellular p53 levels and the activation of p53-dependent transcription. Transcriptional activation of p53 by the CBP TRAM is abolished by wild-type E1A but not by a CBP-binding-deficient E1A mutant.

scholarly journals Sequence analysis of the long control region of human papillomavirus type 16 variants and functional consequences for P97 promoter activity

2000 ◽  
Vol 81 (8) ◽  
pp. 1975-1981 ◽  
Author(s):  
Christina Kämmer ◽  
Ursula Warthorst ◽  
Norah Torrez-Martinez ◽  
Cosette M. Wheeler ◽  
Herbert Pfister
Keyword(s):  
Control Region ◽  
Asian American ◽  
North American ◽  
Promoter Activity ◽  
Tumour Progression ◽  
Human Papillomaviruses ◽  
Long Control Region ◽  
Phylogenetic Groups ◽  
Hpv 16

Genital human papillomaviruses (HPV) are considered to be one of the main risk factors for the development of cervical cancer. The P97 promoter at the E6-proximal end of the long control region (LCR) regulates the transcription of viral genes, especially the oncogenes E6 and E7. The LCR contains binding sites of several viral and cellular transcription factors, which either activate or repress the P97 promoter. Intratype variants of HPV-16 belong to six geographically clustered phylogenetic groups distributed all over the world. These variants exhibit differences in E6 protein activities and in tumour progression in vivo. Seven HPV-16 variants were investigated by sequencing the entire LCR (nt 7060–124) and by comparing the transcriptional activities of their P97 promoters. Previously unknown nucleotide variations were identified in all LCRs investigated. In luciferase assays, 3·3- and 2·8-fold increases in P97 promoter activity were detected in the Asian American c and North American 1 variants when compared with the European reference clone. The African variants 1a and 2a exhibited P97 promoter activities comparable to the European reference clone. After recombining different LCR fragments, the region responsible for enhanced transcription in the Asian American c and North American 1 variants could be attributed to the E6-proximal end of the LCR (nt 7619–124).

scholarly journals Contribution of HDAC3 to transcriptional repression by the human papillomavirus 31 E8^E2 protein

2020 ◽  
Vol 101 (7) ◽  
pp. 751-759
Author(s):  
Marcel Dreer ◽  
Saskia Blondzik ◽  
Elke Straub ◽  
Thomas Iftner ◽  
Frank Stubenrauch
Keyword(s):  
Transcription Factors ◽  
Human Papillomavirus ◽  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Human Papillomaviruses ◽  
Related Protein ◽  
E2 Protein ◽  
Histone Deacetylase 3 ◽  
Cellular Genes ◽  
Cellular Transcription

Human papillomaviruses (HPV) such as HPV16 and HPV31 encode an E8^E2 protein that acts as a repressor of viral replication and transcription. E8^E2′s repression activities are mediated via the interaction with host-cell NCoR (nuclear receptor corepressor)/SMRT (silencing mediator of retinoid and thyroid receptors) corepressor complexes, which consist of NCoR, its homologue SMRT, GPS2 (G-protein pathway suppressor 2), HDAC3 (histone deacetylase 3), TBL1 (transducin b-like protein 1) and its homologue TBLR1 (TBL1-related protein 1). We now provide evidence that transcriptional repression by HPV31 E8^E2 is NCoR/SMRT-dependent but surprisingly always HDAC3-independent when analysing different HPV promoters. This is in contrast to the majority of several cellular transcription factors using NCoR/SMRT complexes whose transcriptional repression activities are both NCoR/SMRT- and HDAC3-dependent. However, NCoR/SMRT-dependent but HDAC3-independent repression has been described for specific cellular genes, suggesting that this may not be specific for HPV promoters but could be a feature of a subset of NCoR/SMRT-HDAC3 regulated genes.

scholarly journals Cellular transcription factors regulate human papillomavirus type 16 gene expression by binding to a subset of the DNA sequences recognized by the viral E2 protein

1999 ◽  
Vol 80 (8) ◽  
pp. 2087-2096 ◽  
Author(s):  
Hannah Lewis ◽  
Kenneth Webster ◽  
Ana-Maria Sanchez-Perez ◽  
Kevin Gaston
Keyword(s):  
Transcription Factors ◽  
Human Papillomavirus ◽  
Dna Sequences ◽  
Hpv 16 ◽  
E2 Protein ◽  
Human Papillomavirus Type 16 ◽  
Binding Factor ◽  
E6 And E7 ◽  
Cellular Transcription ◽  
Site Binding

Human papillomavirus type 16 (HPV-16) is a DNA tumour virus that has been implicated in the development of cervical cancer. The HPV-16 E2 protein binds to four sites that are present upstream of the viral P97 promoter and regulates transcription of the E6 and E7 oncogenes. Here, it is shown that cellular transcription factors bind to two of these E2 sites. One cellular E2 site-binding factor, which is here named CEF-1, binds tightly to E2 site 1. CEF-2, an unrelated cellular E2 site-binding factor, binds tightly to E2 site 3. Transient transfection studies performed in the absence of the E2 protein showed that mutations that blocked the binding of CEF-1 to E2 site 1 or CEF-2 to E2 site 3 significantly reduced P97 promoter activity. Further characterization of CEF-1 indicated that this factor has not previously been identified and that CEF-1 and E2 competed for binding at E2 site 1.

Nuclear Matrix Attachment Regions of Human Papillomavirus Type 16 Point toward Conservation of These Genomic Elements in All Genital Papillomaviruses

1998 ◽  
Vol 72 (5) ◽  
pp. 3610-3622 ◽  
Author(s):  
Shyh-Han Tan ◽  
Dusan Bartsch ◽  
Elisabeth Schwarz ◽  
Hans-Ulrich Bernard
Keyword(s):  
Nuclear Matrix ◽  
Intergenic Region ◽  
Life Cycles ◽  
Human Papillomaviruses ◽  
Matrix Attachment Region ◽  
Nucleotide Sequence Analysis ◽  
Hpv 16 ◽  
Early Late

ABSTRACT The gene functions, transcriptional regulation, and genome replication of human papillomaviruses (HPVs) have been extensively studied. Thus far, however, there has been little research on the organization of HPV genomes in the nuclei of infected cells. As a first step to understand how chromatin and suprachromatin structures may modulate the life cycles of these viruses, we have identified and mapped interactions of HPV DNAs with the nuclear matrix. The endogenous genomes of HPV type 16 (HPV-16) which are present in SiHa, HPKI, and HPKII cells, adhere in vivo to the nuclear matrixes of these cell lines. A tight association with the nuclear matrix in vivo may be common to all genital HPV types, as the genomes of HPV-11, HPV-16, HPV-18, and HPV-33 showed high affinity in vitro to preparations of the nuclear matrix of C33A cells, as did the well-known nuclear matrix attachment region (MAR) of the cellular beta interferon gene. Affinity to the nuclear matrix is not evenly spread over the HPV-16 genome. Five genomic segments have strong MAR properties, while the other parts of the genome have low or no affinity. Some of the five MARs correlate with known cis-responsive elements: a strong MAR lies in the 5′ segment of the long control region (LCR), and another one lies in the E6 gene, flanking the HPV enhancer, the replication origin, and the E6 promoter. The strongest MAR coincides with the E5 gene and the early-late intergenic region. Weak MAR activity is present in the E1 and E2 genes and in the 3′ part of L2. The in vitro map of MAR activity appears to reflect MAR properties in vivo, as we found for two selected fragments with and without MAR activity. As is typical for many MARs, the two segments with highest affinity, namely, the 5′ LCR and the early-late intergenic region, have an extraordinarily high A-T content (up to 85%). It is likely that these MARs have specific functions in the viral life cycle, as MARs predicted by nucleotide sequence analysis, patterns of A-T content, transcription factor YY1 binding sites, and likely topoisomerase II cleavage sites are conserved in similar positions throughout all genital HPVs.

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