References of "Vanderplasschen, Alain"
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See detailInteraction of retroviral Tax oncoproteins with tristetraprolin and regulation of tumor necrosis factor-alpha expression.
Twizere, Jean-Claude ULg; Kruys, Veronique; Lefebvre, Laurent et al

in Journal of the National Cancer Institute (2003), 95(24), 1846-59

BACKGROUND: The Tax oncoproteins are transcriptional regulators of viral expression involved in pathogenesis induced by complex leukemogenic retroviruses (or delta-retroviruses, i.e., primate T-cell ... [more ▼]

BACKGROUND: The Tax oncoproteins are transcriptional regulators of viral expression involved in pathogenesis induced by complex leukemogenic retroviruses (or delta-retroviruses, i.e., primate T-cell leukemia viruses and bovine leukemia virus). To better understand the molecular pathways leading to cell transformation, we aimed to identify cellular proteins interacting with Tax. METHODS: We used a yeast two-hybrid system to identify interacting cellular proteins. Interactions between Tax and candidate interacting cellular proteins were confirmed by glutathione S-transferase (GST) pulldown assays, co-immunoprecipitation, and confocal microscopy. Functional interactions between Tax and one interacting protein, tristetraprolin (TTP), were assessed by analyzing the expression of tumor necrosis factor-alpha (TNF-alpha), which is regulated by TTP, in mammalian cells (HeLa, D17, HEK 293, and RAW 264.7) transiently transfected with combinations of intact and mutant Tax and TTP. RESULTS: We obtained seven interacting cellular proteins, of which one, TTP, was further characterized. Tax and TTP were found to interact specifically through their respective carboxyl-terminal domains. The proteins colocalized in the cytoplasm in a region surrounding the nucleus of HeLa cells. Furthermore, coexpression of Tax was associated with nuclear accumulation of TTP. TTP is an immediate-early protein that inhibits expression of TNF-alpha at the post-transcriptional level. Expression of Tax reverted this inhibition, both in transient transfection experiments and in stably transfected macrophage cell lines. CONCLUSION: Tax, through its interactions with the TTP repressor, indirectly increases TNF-alpha expression. This observation is of importance for the cell transformation process induced by leukemogenic retroviruses, because TNF-alpha overexpression plays a central role in pathogenesis. [less ▲]

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See detailEffect of polystyrene particles on lung mirovascular permeability in isolated perfused rabbit lungs : role of size and surface proporties
Hamoir, J.; Nemmar, A.; Halloy, D. et al

in Toxicology and Applied Pharmacology (2003), 190

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See detailPoxviruses as vaccine vectors
Pastoret, Paul-Pierre ULg; Vanderplasschen, Alain ULg

in Comparative Immunology, Microbiology and Infectious Diseases (2003), 26

The discovery of Jenner in 1798 founded the science of immunology and eventually led to smallpox eradication from the earth in 1980 after a world-wide vaccination campaign with vaccinia virus (another ... [more ▼]

The discovery of Jenner in 1798 founded the science of immunology and eventually led to smallpox eradication from the earth in 1980 after a world-wide vaccination campaign with vaccinia virus (another poxvirus) and paradoxically, despite the eradication of smallpox, there has been an explosion of interest in vaccinia virus in the eighties. This interest has stemmed in part from the application of molecular genetics to clone and express foreign genes from recombinant vaccinia viruses. Vaccinia is also gaining renewed interest due to bioterrorism.These recombinant viruses have multiple applications in research and vaccinology and led to the development of vectored vaccines, such as the recombinant vaccinia rabies vaccine used to eliminate rabies in Western Europe and, more recently, in the United States. Secondly, alternative poxvirus vectors, such as avipox viruses, were proved to be even safer and efficacious non-replicating vectors (suiciole vectors) when used in non-avian species. [less ▲]

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See detailThe core 2 beta-1,6-N-acetylglucosaminyltransferase-mucin encoded by bovine herpesvirus 4 was acquired from an ancestor of the African buffalo
Markine-Goriaynoff, N.; Georgin, J. P.; Goltz, M. et al

in Journal of Virology (2003), 77(3), 1784-1792

The Bo17 gene of bovine herpesvirus 4 (BoHV-4) is the only viral gene known to date that encodes a homologue of the cellular core 2 beta-1,6-N-acetylglucosaminyltransferase-mucin type (C2GnT-M). To ... [more ▼]

The Bo17 gene of bovine herpesvirus 4 (BoHV-4) is the only viral gene known to date that encodes a homologue of the cellular core 2 beta-1,6-N-acetylglucosaminyltransferase-mucin type (C2GnT-M). To investigate the origin and evolution of the Bo17 gene, we analyzed its distribution among BoHV-4 strains and determined the sequences of Bo17 from nine representative strains and of the C2GnT-M gene from six species of ruminants expected to encompass the group within which the gene acquisition occurred. Of 34 strains of BoHV-4, isolated from four different continents, all were found to contain the Bo17 gene. Phylogenetic analyses indicated that Bo17 was acquired from a recent ancestor of the African buffalo, implying that cattle subsequently acquired BoHV-4 by cross-species transmission. The rate of synonymous nucleotide substitution in Bo17 was estimated at 5 x 10(-8) to 6 x 10(-8) substitutions/site/year, consistent with previous estimates made under the assumption that herpesviruses have cospeciated with their hosts. The Bo17 gene acquisition was dated to around 1.5 million years ago. Bo17 sequences from BoHV-4 strains from African buffalo and from cattle formed two separate clades, estimated to have split about 700,000 years ago. Analysis of the ratio of nonsynonymous to synonymous nucleotide substitutions revealed a burst of amino acid replacements subsequent to the transfer of the cellular gene to the viral genome, followed by a return to a strong constraint on nonsynonymous changes during the divergence of contemporary BoHV-4 strains. The Bo17 gene represents the most recent of the known herpesvirus gene acquisitions and provides the best opportunity for learning more about this important process of viral evolution. [less ▲]

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See detailL’herpèsvirus bovin 4
Markine-Goriaynoff, N.; Minner, F.; De Fays, K. et al

in Annales de Médecine Vétérinaire (2003), 147(4), 215-247

Bovine herpesvirus 4 (BoHV-4) belongs to the Herpesviridae family, Gammaherpesvirinae subfamily, Rhadinovirus genus like human herpesvirus 8 (HHV-8), the causative agent of Kaposi's sarcoma. BoHV-4 has a ... [more ▼]

Bovine herpesvirus 4 (BoHV-4) belongs to the Herpesviridae family, Gammaherpesvirinae subfamily, Rhadinovirus genus like human herpesvirus 8 (HHV-8), the causative agent of Kaposi's sarcoma. BoHV-4 has a worldwide distribution in the cattle population. It has been isolated from cattle showing various clinical signs as well as from healthy cattle. The interest of the scientific community for BoHV-4 is explained by two reasons. Firstly, BoHV-4 represents an homologous virus/host species model to study the biology of gammaherpesviruses. Secondly, the use of BoHV-4 as a recombinant vector for expression both in vitro and in vivo has been proposed. For these reasons, a considerable amount of data has been collected on this virus. In the present paper, the authors will present a general overview of the literature published on this virus addressing clinical, epidemiological and fundamental aspects of BoHV-4. Finally, in the light of their recent phylogenetic data, the authors will discuss the origin and the host species of BoHV-4 leading to the conclusion that this virus should be considered as a virus of the African buffalo rather than cattle. [less ▲]

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See detailSTAT5 promotes granulocyte survival during inflammation
Fievez, Laurence ULg; Desmet, Christophe ULg; Pajak, B. et al

Poster (2003)

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See detailThe Uses of Poxviruses as Vectors
Vanderplasschen, Alain ULg; Pastoret, Paul-Pierre ULg

in Current Gene Therapy (2003), 3(6), 583-95

Poxviruses have played an amazing role in the development of virology, immunology and vaccinology. In 1796, deliberate inoculation of cowpox virus to humans was proved by Dr. Edward Jenner to protect ... [more ▼]

Poxviruses have played an amazing role in the development of virology, immunology and vaccinology. In 1796, deliberate inoculation of cowpox virus to humans was proved by Dr. Edward Jenner to protect against the antigenically related smallpox virus (variola). This discovery founded the science of immunology and eventually led to smallpox eradication from the earth in 1980 after a world wide vaccination campaign with vaccinia virus (another poxvirus). Paradoxically, despite the eradication of smallpox, there has been an explosion of interest in vaccinia virus in the eighties. This interest has stemmed in part from the application of molecular genetics to clone and express foreign genes from recombinant vaccinia virus. The use of these recombinant vaccinia viruses as efficacious in vitro expression system and live vaccine has raised concerns about their safety. The work of the scientific community of the last 20 years has contributed to improve drastically the safety of poxvirus derived vectors. Firstly, the safety of vaccinia virus has been enhanced by production of genetically attenuated strains. Secondly, alternative poxvirus vectors, such as avipoxviruses, were proved to be extremely safe and efficacious non-replicating vectors when used in non avian species. In the present chapter, the basic concepts of poxvirus biology required to assess the safety of a poxvirus derived vector are provided. The principal poxvirus vectors available to date are described in regards to their biosafety. [less ▲]

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See detailNew anticomplement polypeptide from salivary glands of the tick Ixodes Ricinus
Daix, V.; Godfroid, E.; Pastoret, Paul-Pierre ULg et al

in PCT WO (2003), (03/002734 A1),

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See detailGlycoprotein G isoforms from some alphaherpesviruses function as broad-spectrum chemokine binding proteins
Bryant, N. A.; Davis-Poynter, N.; Vanderplasschen, Alain ULg et al

in EMBO Journal (2003), 22

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See detailA proinflammatory role for the cyclopentenone prostaglandins at low micromolar concentrations: Oxidative stress-induced extracellular signal-regulated kinase activation without NF-kappa B inhibition
Bureau, Fabrice ULg; Desmet, Christophe ULg; Burin Kefer, D. et al

in Journal of Immunology (2002), 168(10), 5318-5325

An anti-inflammatory role and therapeutic potential for cyclopentenone PGs (cyPGs) has been suggested, based on observations that levels of cyPGs in exudates increase during the resolution phase of ... [more ▼]

An anti-inflammatory role and therapeutic potential for cyclopentenone PGs (cyPGs) has been suggested, based on observations that levels of cyPGs in exudates increase during the resolution phase of inflammation, and that exogenous cyPGs may attenuate the inflammatory response in vivo and in vitro mainly through inhibition of NF-kappaB, a critical activator of inflammatory gene expression. However, exogenous cyPGs inhibit NF-kappaB only at concentrations substantially higher than those of endogenous cyPGs present in inflammatory fluids, thus challenging the hypothesis that cyPGs are naturally occurring inhibitors of inflammation and suggesting that cyPGs at low concentrations might have previously unappreciated effects. In this study, using various cell types, we report that cyPGs, when used at concentrations substantially lower than required for NF-kappaB inhibition (viz, low micromolar concentrations), significantly potentiate the inflammatory response to TNF-alpha. At these concentrations, cyPGs induce production of reactive oxygen species, thereby synergizing with TNF-alpha to activate the extracellular signal-regulated kinase 1/2, an activation which in turn potentiates proinflammatory cytokine expression at both transcriptional and posttranscriptional levels. Our studs establishes a proinflammatory role for cyPGs at low micromolar concentrations, raises the possibility that cyPGs do not act as physiologic anti-inflammatory mediators, and questions the therapeutic potential of these compounds. [less ▲]

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See detailConstitutive nuclear factor-kappa B activity preserves homeostasis of quiescent mature lymphocytes and granulocytes by controlling the expression of distinct Bcl-2 family proteins
Bureau, Fabrice ULg; Vanderplasschen, Alain ULg; Jaspar, Fabrice ULg et al

in Blood (2002), 99(10), 3683-3691

Constitutive nuclear factor kappaB (NFkappaB) activity protects quiescent mature Immune cells from spontaneous apoptosis. Here, we examined whether NF-kappaB exerts its antiapoptotic function in these ... [more ▼]

Constitutive nuclear factor kappaB (NFkappaB) activity protects quiescent mature Immune cells from spontaneous apoptosis. Here, we examined whether NF-kappaB exerts its antiapoptotic function in these cells through the control of Bcl-2 family proteins. Specific pharmacologic inhibitors of NF-kappaB were used to achieve total NF-kappaB inactivation In quiescent human blood lymphocytes, granulocytes, and monocytes. NF-kappaB inhibition induced drastic lymphocyte and granulocyte apoptosis, but only moderate monocyte apoptosis. T- and B-cell apoptosis was slow and associated with a gradual down-regulation of the prosurvival Bcl-2 family proteins Bcl-X-L and BcI-2, respectively. By contrast, granulocyte apoptosis was fast and accompanied by a rapid cellular accumulation of Bcl-x(s), the proapoptotic Bcl-x isoform that is generated from alternative splicing of the bcl-x pre-mRNA. Finally, antisense bci-x(L) and bcl-2 knockdown in T and B cells, respectively, and induction of Bcl-xs expression in granulocytes through antisense oligonucleotide-mediated redirection of bcl-x pre-mRNA splicing were sufficient to induce significant apoptosis in these cells. Taken together, these results reveal that basal NF-kappaB activity preserves homeostasis of quiescent mature lymphocytes and granulocytes through regulation of distinct members of the Bcl-2 family. This study sheds light on the constitutive mechanisms by which NF-kappaB maintains defense integrity. (C) 2002 by The American Society of Hematology. [less ▲]

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See detailOncoviral bovine leukemia virus G4 and human T-cell leukemia virus type 1 p13(II) accessory proteins interact with farnesyl pyrophosphate synthetase
Lefebvre, Laurent; Vanderplasschen, Alain ULg; Ciminale, Vincenzo et al

in Journal of Virology (2002), 76(3), 1400-1414

G4 and p13(II) are accessory proteins encoded by the X region of bovine leukemia virus and human T-cell leukemia virus type 1 (HTLV-1), respectively. Disruption of the G4 and p13(II) open reading frames ... [more ▼]

G4 and p13(II) are accessory proteins encoded by the X region of bovine leukemia virus and human T-cell leukemia virus type 1 (HTLV-1), respectively. Disruption of the G4 and p13(II) open reading frames interferes with viral spread in animal model systems, indicating that the corresponding proteins play a key role in viral replication. In addition, G4 is oncogenic in primary cell cultures and is absolutely required for efficient onset of leukemogenesis in sheep. To gain insight into the function of these proteins, we utilized the yeast two-hybrid system to identify protein partners of G4. Results revealed that G4 interacts with farnesyl pyrophosphate synthetase (FPPS), a protein involved in the mevalonate/squalene pathway and in synthesis of FPP, a substrate required for prenylation of Ras. The specificity of the interaction was verified by glutathione S-transferase (GST) pull-down assays and by coimmunoprecipitation experiments. Furthermore, confocal microscopy showed that the subcellular localization of G4 was profoundly affected by FPPS. The G4 protein itself was not prenylated, at least in rabbit reticulocyte lysate-based assays. The domain of G4 required for binding to FPPS was restricted to an amphipathic alpha-helix rich in arginine residues. Subtle mutation of this alpha-helix abrogated G4 oncogenic potential in vitro, providing a biological relevance for FPPS-G4 complex formation in cells. Finally, HTLV-1 p13(II) was also found to specifically interact with FPPS (in yeast as well as in GST pull-down assays) and to colocalize with G4 in mitochondria, suggesting a functional analogy between these oncoviral accessory proteins. Identification of FPPS as a molecular partner for p13(II) and G4 accessory proteins opens retrovirus-induced leukemia. [less ▲]

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See detailCD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: possible involvement in allergic inflammation
Bureau, Fabrice ULg; Seumois, G.; Jaspar, F. et al

in Pflügers Archiv : European Journal of Physiology (2002), 443

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See detailCyclopentenone prostaglandins at low concetrations exert pro-inflammatory effects through oxidative stress-induced ERK1/2 activation
Bureau, Fabrice ULg; Desmet, Christophe ULg; Mélotte, C. et al

in Proceedings: Spring Meeting of the Belgian Society of Physiology and Pharmacology (2002)

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See detailCD40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: Possible involvement in allergic inflammation.
Bureau, Fabrice ULg; Seumois, Gregory; Jaspar, Fabrice et al

in Journal of Allergy and Clinical Immunology (The) (2002), 110(3), 443-9

BACKGROUND: CD40 engagement enhances eosinophil survival, suggesting a role for this receptor in the development of eosinophilia. OBJECTIVE: We examined whether CD40 enhances eosinophil survival by ... [more ▼]

BACKGROUND: CD40 engagement enhances eosinophil survival, suggesting a role for this receptor in the development of eosinophilia. OBJECTIVE: We examined whether CD40 enhances eosinophil survival by inducing the expression of antiapoptotic proteins. Three members of the inhibitor of apoptosis protein (IAP) family, namely cellular (c)-IAP1, c-IAP2, and XIAP, and 2 antiapoptotic proteins of the Bcl-2 family, namely Bcl-x(L) and Bfl-1/A1, were investigated. METHODS: Blood and sputum were obtained from healthy subjects and atopic asthmatic patients. Blood eosinophils were isolated by means of magnetic selection. Expression of CD40, IAPs, and Bcl-2 proteins was investigated by using flow cytometry, immunoblotting, or both. CD40 stimulation was achieved with agonistic antibodies or soluble ligands. Apoptosis was assessed by staining with propidium iodide and FITC-conjugated annexin-V. c-IAP2 expression was inhibited with antisense oligonucleotides. RESULTS: Freshly isolated eosinophils from healthy and asthmatic patients did not express CD40. Conversely, eosinophils expressed CD40 spontaneously when cultured for 48 hours. At this time point, CD40 stimulation significantly delayed eosinophil apoptosis. Inhibition of eosinophil apoptosis was accompanied by induction of c-IAP2 but not c-IAP1, XIAP, Bcl-x(L), or Bfl-1/A1 expression. Antisense knockdown of c-iap2 abolished CD40-induced enhancement of eosinophil survival. Sputum cells from asthmatic patients, unlike those from healthy subjects, substantially expressed CD40 and c-IAP2. Moreover, a strong correlation was found between the percentage of eosinophils in the sputum from asthmatic patients and the sputum level of CD40 and c-IAP2 expression. CONCLUSION: The results demonstrate that CD40 engagement enhances eosinophil survival through induction of c-IAP2 expression and suggest a role for this mechanism in allergic inflammation. [less ▲]

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See detailA pro-inflammatory role for the cyclopentenone prostaglandins at low concentrations: oxidative stress-induced ERK activation without NFKB inhibition
Bureau, Fabrice ULg; Desmet, Christophe ULg; Melotte, D. et al

in Proceedings : Congress "Cell signaling, transcription and translation as therapeutics targets" (2002)

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See detailLocal administration of nuclear factor-kB decoy oligodeoxinucleotides prevents allergic airway inflammation
Bureau, Fabrice ULg; Gosset, P.; Desmet, Christophe ULg et al

in 12th European Respiratory Society Annual Congress (2002)

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See detailThe formation and function of extracellular enveloped vaccinia virus
Smith, G. L.; Vanderplasschen, Alain ULg; Law, M.

in Journal of General Virology (The) (2002), 83

Vaccinia virus produces four different types of virion from each infected cell called intracellular mature virus (IMV), intracellular enveloped virus (IEV), cell-associated enveloped virus (CEV) and ... [more ▼]

Vaccinia virus produces four different types of virion from each infected cell called intracellular mature virus (IMV), intracellular enveloped virus (IEV), cell-associated enveloped virus (CEV) and extracellular enveloped virus (EEV). These virions have different abundance, structure, location and roles in the virus life-cycle. Here, the formation and function of these virions are considered with emphasis on the EEV form and its precursors, IEV and CEV. IMV is the most abundant form of virus and is retained in cells until lysis; it is a robust, stable virion and is well suited to transmit infection between hosts. IEV is formed by wrapping of IMV with intracellular membranes, and is an intermediate between IMV and CEV/EEV that enables efficient virus dissemination to the cell surface on microtubules. CEV induces the formation of actin tails that drive CEV particles away from the cell and is important for cell-to-cell spread. Lastly, EEV mediates the long-range dissemination of virus in cell culture and, probably, in vivo. Seven virus-encoded proteins have been identified that are components of IEV, and five of them are present in CEV or EEV. The roles of these proteins in virus morphogenesis and dissemination, and as targets for neutralizing antibody are reviewed. The production of several different virus particles in the VV replication cycle represents a coordinated strategy to exploit cell biology to promote virus spread and to aid virus evasion of antibody and complement. [less ▲]

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