scholarly journals Brd4 Is Involved in Multiple Processes of the Bovine Papillomavirus Type 1 Life Cycle

2006 ◽  
Vol 80 (7) ◽  
pp. 3660-3665 ◽  
Author(s):  
Ivar Ilves ◽  
Kristina Mäemets ◽  
Toomas Silla ◽  
Kadri Janikson ◽  
Mart Ustav
Keyword(s):  
Life Cycle ◽  
Transcription Activation ◽  
Bovine Papillomavirus ◽  
Viral Genomes ◽  
Therapeutic Value ◽  
Multiple Processes ◽  
Chromosome Attachment ◽  
Dependent Mechanism

ABSTRACT Brd4 protein has been proposed to act as a cellular receptor for the bovine papillomavirus type 1 (BPV1) E2 protein in the E2-mediated chromosome attachment and mitotic segregation of viral genomes. Here, we provide data that show the involvement of Brd4 in multiple early functions of the BPV1 life cycle, suggest a Brd4-dependent mechanism for E2-dependent transcription activation, and indicate the role of Brd4 in papillomavirus and polyomavirus replication as well as cell-specific utilization of Brd4-linked features in BPV1 DNA replication. Our data also show the potential therapeutic value of the disruption of the E2-Brd4 interaction for the development of antiviral drugs.

scholarly journals Structure, Function, and Interactions of the HIV-1 Capsid Protein

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 100
Author(s):  
Eric Rossi ◽  
Megan E. Meuser ◽  
Camille J. Cunanan ◽  
Simon Cocklin
Keyword(s):  
Life Cycle ◽  
Capsid Protein ◽  
Adaptor Proteins ◽  
Restriction Factors ◽  
Gag Polyprotein ◽  
Immunodeficiency Virus ◽  
Host Cell Factors ◽  
Hiv 1

The capsid (CA) protein of the human immunodeficiency virus type 1 (HIV-1) is an essential structural component of a virion and facilitates many crucial life cycle steps through interactions with host cell factors. Capsid shields the reverse transcription complex from restriction factors while it enables trafficking to the nucleus by hijacking various adaptor proteins, such as FEZ1 and BICD2. In addition, the capsid facilitates the import and localization of the viral complex in the nucleus through interaction with NUP153, NUP358, TNPO3, and CPSF-6. In the later stages of the HIV-1 life cycle, CA plays an essential role in the maturation step as a constituent of the Gag polyprotein. In the final phase of maturation, Gag is cleaved, and CA is released, allowing for the assembly of CA into a fullerene cone, known as the capsid core. The fullerene cone consists of ~250 CA hexamers and 12 CA pentamers and encloses the viral genome and other essential viral proteins for the next round of infection. As research continues to elucidate the role of CA in the HIV-1 life cycle and the importance of the capsid protein becomes more apparent, CA displays potential as a therapeutic target for the development of HIV-1 inhibitors.

scholarly journals Proinsulin C-peptide - A Consensus Statement

2001 ◽  
Vol 2 (2) ◽  
pp. 145-151 ◽  
Author(s):  
Anders A. F. Sima ◽  
George Grunberger ◽  
Hans Jörnvall ◽  
John Wahren ◽  
The C-Peptide Study Group
Keyword(s):  
Physiological Role ◽  
Biological Action ◽  
Clinical Effects ◽  
State University ◽  
C Peptide ◽  
Wayne State University ◽  
Therapeutic Value ◽  
Diabetes Center

In recent years the physiological role of the proinsulin C-peptide has received increasing attention, focusing on the potential therapeutic value of C-peptide replacement in preventing and ameliorating type 1 diabetic complications. In order to consolidate these new data and to identify the immediate directions of C-peptide research and its clinical usefulness, an International Symposium was held in Detroit, Michigan, on October 20–21, 2000, under the auspices of the Wayne State University/Morris Hood Jr. Comprehensive Diabetes Center. In this communication, we review the cellular, physiological and clinical effects of C-peptide replacement in animal models and in patients with type 1 diabetes. Finally, recommendations are presented as to the most urgent studies that should be pursued to further establish the biological action of C-peptide and its therapeutic value.

scholarly journals Transformation by Bovine Papillomavirus Type 1 E6 Requires Paxillin

2008 ◽  
Vol 82 (12) ◽  
pp. 5962-5966 ◽  
Author(s):  
Ramon Wade ◽  
Nicole Brimer ◽  
Scott Vande Pol
Keyword(s):  
Focal Adhesion ◽  
Essential Role ◽  
Consensus Sequence ◽  
Cellular Protein ◽  
Regulatory Proteins ◽  
Phosphorylation Sites ◽  
Bovine Papillomavirus ◽  
Independent Transformation

ABSTRACT Papillomavirus E6 proteins are adapters that change the function of cellular regulatory proteins. The bovine papillomavirus type 1 E6 (BE6) binds to LXXLL peptide sequences termed LD motifs (consensus sequence LDXLLXXL) on the cellular protein paxillin that is a substrate of Src and focal adhesion kinases. Anchorage-independent transformation induced by BE6 required both paxillin and BE6-binding LD motifs on paxillin but was independent of the major tyrosine phosphorylation sites of paxillin. The essential role of paxillin in transformation by BE6 highlights the role of paxillin in the transduction of cellular signals that result in anchorage-independent cell proliferation.

scholarly journals p38 mitogen-activated protein kinase is crucial for bovine papillomavirus type-1 transformation of equine fibroblasts

2011 ◽  
Vol 92 (8) ◽  
pp. 1778-1786 ◽  
Author(s):  
ZhengQiang Yuan ◽  
Elizabeth A. Gault ◽  
M. Saveria Campo ◽  
Lubna Nasir
Keyword(s):  
Protein Kinase ◽  
Viral Gene Expression ◽  
Cellular Transformation ◽  
Mitogen Activated Protein Kinase ◽  
Viral Gene ◽  
Bovine Papillomavirus ◽  
Equine Sarcoid ◽  
Mitogen Activated Protein

Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type-1 (BPV-1) and less commonly BPV-2 are the causative agents of the diseases. It has been demonstrated that BPV-1 viral gene expression is necessary for maintaining the transformation phenotype. However, the underlying mechanism for BPV-1 transformation remains largely unknown, and the cellular factors involved in transformation are not fully understood. Previously mitogen-activated protein kinase (MAPK) signalling pathway has been shown to be important for cellular transformation. This study investigated the role of p38 MAPK (p38) in the transformation of equine fibroblasts by BPV-1. Elevated expression of phosphorylated p38 was observed in BPV-1 expressing fibroblasts due to the expression of BPV-1 E5 and E6. The phosphorylation of the MK2 kinase, a substrate of p38, was also enhanced. Inhibition of p38 activity by its selective inhibitor SB203580 changed cell morphology, reduced the proliferation of sarcoid fibroblasts and inhibited cellular invasiveness, indicating the indispensable role of p38 in BPV-1 transformation of equine fibroblasts. These findings provide new insights into the pathogenesis of equine sarcoids and suggest that p38 could be a potential target for equine sarcoid therapy.

Detection and characterization of viral genomes and search for tumoral antigens in two hamster cell lines derived from tumors induced by bovine papillomavirus type 1

1981 ◽  
Vol 27 (5) ◽  
pp. 693-702 ◽  
Author(s):  
FrançOise Breitburd ◽  
Michel Favre ◽  
Rima Zoorob ◽  
Dominique Fortin ◽  
Gérard Orth
Keyword(s):  
Cell Lines ◽  
Bovine Papillomavirus ◽  
Viral Genomes

scholarly journals Bovine Papillomavirus Type 1 Infection Is Mediated by SNARE Syntaxin 18

2007 ◽  
Vol 81 (14) ◽  
pp. 7435-7448 ◽  
Author(s):  
Valerie Laniosz ◽  
Kha C. Nguyen ◽  
Patricio I. Meneses
Keyword(s):  
Viral Infections ◽  
Major Capsid Protein ◽  
Target Cells ◽  
Bovine Papillomavirus ◽  
Snare Protein ◽  
Golgi Compartment ◽  
L1 And L2

ABSTRACT Events that lead to viral infections include the binding of the virus to the target cells, internalization of the virus into the cells, and the ability of the viral genome to be expressed. These steps are mediated by cellular and viral proteins and are temporally regulated. The papillomavirus capsid consists of two virally encoded capsid proteins, L1 and L2. Much is known about the role of the major capsid protein L1 compared to what is known of the role of the L2 protein. We identified the interaction of the L2 protein with SNARE protein syntaxin 18, which mediates the trafficking of vesicles and their cargo between the endoplasmic reticulum, the cis-Golgi compartment, and possibly the plasma membrane. Mutations of L2 residues 41 to 44 prevented the interaction of L2 protein with syntaxin 18 in cotransfection experiments and resulted in noninfectious pseudovirions. In this paper, we describe that syntaxin 18 colocalizes with infectious bovine papillomavirus type 1 (BPV1) pseudovirions during infection but does not colocalize with the noninfectious BPV1 pseudovirions made with an L2 mutant at residues 41 to 44. We show that an antibody against BPV1 L2 residues 36 to 49 (αL2 36-49) binds to in vitro-generated BPV1 pseudoviral capsids and does not coimmunoprecipitate syntaxin 18- and BPV1 L2-transfected proteins. αL2 36-49 was able to partially or completely neutralize infection of BPV1 pseudovirions and genuine virions. These results support the dependence of syntaxin 18 during BPV1 infection and the ability to interfere with infection by targeting the L2-syntaxin 18 interaction and further define the infectious route of BPV1 mediated by the L2 protein.

Bovine Papillomavirus Type 1 Genomes and the E2 Transactivator Protein Are Closely Associated with Mitotic Chromatin

1998 ◽  
Vol 72 (3) ◽  
pp. 2079-2088 ◽  
Author(s):  
Mario H. Skiadopoulos ◽  
Alison A. McBride
Keyword(s):  
Bovine Papillomavirus ◽  
Transactivation Domain ◽  
Mitotic Chromosomes ◽  
Viral Genomes ◽  
Binding Function ◽  
Dividing Cells ◽  
Transactivator Protein ◽  
Episomal Maintenance ◽  
Mitotic Chromatin

ABSTRACT The bovine papillomavirus type 1 E2 transactivator protein is required for viral transcriptional regulation and DNA replication and may be important for long-term episomal maintenance of viral genomes within replicating cells (M. Piirsoo, E. Ustav, T. Mandel, A. Stenlund, and M. Ustav, EMBO J. 15:1–11, 1996). We have evidence that, in contrast to most other transcriptional transactivators, the E2 transactivator protein is associated with mitotic chromosomes in dividing cells. The shorter E2-TR and E8/E2 repressor proteins do not bind to mitotic chromatin, and the N-terminal transactivation domain of the E2 protein is necessary for the association. However, the DNA binding function of E2 is not required. We have found that bovine papillomavirus type 1 genomes are also associated with mitotic chromosomes, and we propose a model in which E2-bound viral genomes are transiently associated with cellular chromosomes during mitosis to ensure that viral genomes are segregated to daughter cells in approximately equal numbers.

scholarly journals Optimization of a Weak 3′ Splice Site Counteracts the Function of a Bovine Papillomavirus Type 1 Exonic Splicing Suppressor In Vitro and In Vivo

2000 ◽  
Vol 74 (13) ◽  
pp. 5902-5910 ◽  
Author(s):  
Zhi-Ming Zheng ◽  
Jesse Quintero ◽  
Eric S. Reid ◽  
Christian Gocke ◽  
Carl C. Baker
Keyword(s):  
Alternative Splicing ◽  
Splice Site ◽  
Splicing Factors ◽  
Bovine Papillomavirus ◽  
Splicing Pattern ◽  
In Vitro Splicing

ABSTRACT Alternative splicing is a critical component of the early to late switch in papillomavirus gene expression. In bovine papillomavirus type 1 (BPV-1), a switch in 3′ splice site utilization from an early 3′ splice site at nucleotide (nt) 3225 to a late-specific 3′ splice site at nt 3605 is essential for expression of the major capsid (L1) mRNA. Three viral splicing elements have recently been identified between the two alternative 3′ splice sites and have been shown to play an important role in this regulation. A bipartite element lies approximately 30 nt downstream of the nt 3225 3′ splice site and consists of an exonic splicing enhancer (ESE), SE1, followed immediately by a pyrimidine-rich exonic splicing suppressor (ESS). A second ESE (SE2) is located approximately 125 nt downstream of the ESS. We have previously demonstrated that the ESS inhibits use of the suboptimal nt 3225 3′ splice site in vitro through binding of cellular splicing factors. However, these in vitro studies did not address the role of the ESS in the regulation of alternative splicing. In the present study, we have analyzed the role of the ESS in the alternative splicing of a BPV-1 late pre-mRNA in vivo. Mutation or deletion of just the ESS did not significantly change the normal splicing pattern where the nt 3225 3′ splice site is already used predominantly. However, a pre-mRNA containing mutations in SE2 is spliced predominantly using the nt 3605 3′ splice site. In this context, mutation of the ESS restored preferential use of the nt 3225 3′ splice site, indicating that the ESS also functions as a splicing suppressor in vivo. Moreover, optimization of the suboptimal nt 3225 3′ splice site counteracted the in vivo function of the ESS and led to preferential selection of the nt 3225 3′ splice site even in pre-mRNAs with SE2 mutations. In vitro splicing assays also showed that the ESS is unable to suppress splicing of a pre-mRNA with an optimized nt 3225 3′ splice site. These data confirm that the function of the ESS requires a suboptimal upstream 3′ splice site. A surprising finding of our study is the observation that SE1 can stimulate both the first and the second steps of splicing.

Sign in / Sign up

Export Citation Format

Share Document