References of "Vanderplasschen, Alain"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailThe A3 gene of Alcelaphine herpesvirus 1 encodes a viral semaphorin that is non-essential for the induction of malignant catarrhal fever
Myster, Françoise ULg; Palmeira, Leonor ULg; Vanderplasschen, Alain ULg et al

Conference (2010, November)

Alcelaphine herpesvirus 1 (AlHV-1) is a γ-Herpesvirus carried by wildebeest asymptomatically. AlHV-1 is however responsible for the development of malignant catarrhal fever (MCF) when cross-species ... [more ▼]

Alcelaphine herpesvirus 1 (AlHV-1) is a γ-Herpesvirus carried by wildebeest asymptomatically. AlHV-1 is however responsible for the development of malignant catarrhal fever (MCF) when cross-species transmitted to a variety of ruminant susceptible species. Wildebeest-derived (WD)-MCF is a frequently fatal lymphoproliferative and degenerative disease of ruminants. Experimentally, WD-MCF can be reproduced in rabbits. The A3 open reading frame (ORF) of the AlHV-1 encodes a putative semaphorin homolog protein, thereafter named AlHV-sema. Semaphorins are secreted and membrane-associated proteins characterized by a conserved amino-terminal ‘Sema’ domain. Initially identified as guidance factors that assist axons pathfinding during neural development, semaphorins have been shown over the last decade to have significant functions in various processes of immunoregulation. Bioinformatics analyses revealed that AlHV-sema has a high homology to the cellular Sema7A. Besides its roles in neural development, Sema7A has been shown to play pivotal functions in the regulation of cytokine secretion and as a tumor suppressor. In order to investigate whether AlHV-Sema could play a role in the pathogenesis of WD-MCF, we used the AlHV-1 BAC clone and produced a strain deleted for A3 and a revertant strain. The strain deleted for A3 replicated comparably to the wild-type parental strain in vitro. In vivo, rabbits infected with the strain deleted for A3 developed WD-MCF similarly to that observed with the parental strain with both severely increased CD8+ T cell frequencies and viral genomic charge over time in peripheral blood and in lymph nodes at time of death, as well as indistinguishable histopathological lesions in lymphoid organs and in liver, lung and kidney. In conclusion, this study demonstrates that AlHV-sema is not essential for the induction of WD-MCF in rabbits. [less ▲]

Detailed reference viewed: 41 (8 ULg)
Full Text
See detailTargeting nanoparticles to M cells with non-peptidic ligands for oral vaccination
Freichels, Hélène ULg; Fievez, Virginie; Plapied, Laurence et al

Poster (2010, March 18)

Detailed reference viewed: 38 (6 ULg)
Full Text
Peer Reviewed
See detailComparative study of Murid gamma-herpesvirus 4 infection in mice and in a natural host, the bank voles.
François, Sylvie ULg; Vidick, Sarah ULg; Sarlet, Michaël ULg et al

in Journal of General Virology (The) (2010)

Gamma-herpesviruses are archetypal pathogenic persistent viruses. The known human gamma-herpesviruses (Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus) are host-specific and therefore lack ... [more ▼]

Gamma-herpesviruses are archetypal pathogenic persistent viruses. The known human gamma-herpesviruses (Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus) are host-specific and therefore lack a convenient in vivo infection model. This makes related animal gamma-herpesviruses an important source of information. We are studying Murid herpesvirus 4 (MuHV-4), a virus originally isolated from bank voles (Myodes glareolus). MuHV-4 infection of inbred laboratory mouse strains (Mus musculus) is commonly used as a general model of gamma-herpesvirus pathogenesis. However, MuHV-4 has not been isolated from house mice, and no systematic comparison has been made between experimental MuHV-4 infections of mice and bank voles. We have therefore characterized MuHV-4 (strain MHV-68) infection of bank voles, both through global luciferase imaging and through classical virological methods. As in mice, intranasal virus inoculation led to productive replication in bank vole lungs, accompanied by massive cellular infiltrates. However, the extent of lytic virus replication was ~1000 fold lower in bank voles than in mice. Peak latency titers in lymphoid tissue were also lower, although latency was still established. Finally, we tested viral transmission between animals maintained in captivity. However, as observed in mice, MuHV-4 did not transmit between voles in these conditions. In conclusion, this study revealed that despite quantitative differences, replication and latency sites of MuHV-4 are comparable in bank voles and in mice. It appears therefore so far that Mus musculus represents a suitable host for studying gamma-herpesvirus pathogenesis with MuHV-4. Establishing transmission conditions in captivity will be a vital step for further research in that field. [less ▲]

Detailed reference viewed: 83 (33 ULg)
Full Text
Peer Reviewed
See detailCyprinid herpesvirus 3
Michel, Benjamin; Fournier, Guillaume; Lieffrig, François et al

in Emerging Infectious Diseases (2010), 16

Detailed reference viewed: 11 (1 ULg)
Full Text
Peer Reviewed
See detailThe genome of cyprinid herpesvirus 3 encodes 40 proteins incorporated in mature virions
Michel, Benjamin ULg; Leroy, B.; Victor, Stalinraj ULg et al

in Journal of General Virology (The) (2010)

Detailed reference viewed: 48 (22 ULg)
Full Text
Peer Reviewed
See detailBCL-3 degradation involves its polyubiquitination through a FBW7-independent pathway and its binding to the proteasome subunit PSMB1.
Keutgens, Aurore ULg; Zhang-Shao, Xin ULg; Shostak, Kateryna ULg et al

in Journal of Biological Chemistry (2010), 285(33), 2583125840

The oncogenic protein BCL-3 activates or represses gene transcription through binding with the NF-kappaB proteins p50 and p52 and is degraded through a phospho- and GSK3-dependent pathway. However, the ... [more ▼]

The oncogenic protein BCL-3 activates or represses gene transcription through binding with the NF-kappaB proteins p50 and p52 and is degraded through a phospho- and GSK3-dependent pathway. However, the mechanisms underlying its degradation remain poorly understood. Yeast-two-hybrid analysis led to the identification of the proteasome subunit PSMB1 as a BCL-3-associated protein. The binding of BCL-3 to PSMB1 is required for its degradation through the proteasome. Indeed, PSMB1-depleted cells are defective in degrading polyubiquitinated BCL-3. The N-terminal part of BCL-3 includes lysines 13 and 26 required for the K48-linked polyubiquitination of BCL-3. Moreover, the E3 ligase FBW7 known to polyubiquitinate a variety of substrates phosphorylated by GSK3 is dispensable for BCL-3 degradation. Thus, our data defined an unique motif of BCL-3 that is needed for its recruitment to the proteasome and identified PSMB1 as a key protein required for the proteasome-mediated degradation of a nuclear and oncogenic IkappaB protein. [less ▲]

Detailed reference viewed: 79 (36 ULg)
Full Text
Peer Reviewed
See detailBovine herpesvirus 4 ORF73 is dispensable for viral growth in vitro but is essential for viral persistence in vivo.
Thirion, M.; Machiels, Bénédicte ULg; Farnir, Frédéric ULg et al

in Journal of General Virology (The) (2010), 91(10), 2574-84

ORF73 orthologues encoded by different rhadinoviruses have been studied extensively. These studies revealed that the ORF73 expression product (pORF73) is a multifunctional protein essential for latency ... [more ▼]

ORF73 orthologues encoded by different rhadinoviruses have been studied extensively. These studies revealed that the ORF73 expression product (pORF73) is a multifunctional protein essential for latency that enables episome tethering to mitotic chromosomes and modulates cellular pathways implicated in growth and survival of latently infected cells. Comparison of pORF73 orthologues encoded by rhadinoviruses reveals important variations in amino acid sequence length and composition. Bovine herpesvirus 4 (BoHV-4) encodes by far the shortest ORF73 orthologue with a size equivalent to only 22% of the largest orthologues. The present study focused on determining if BoHV 4 ORF73 is a bona fide gene and investigating whether it is essential for latency as established for larger ORF73 orthologues. Our results demonstrate that BoHV-4 ORF73 is transcribed as immediate-early bicistronic mRNA together with ORF71. Using a BoHV-4 bacterial artificial chromosome clone, we produced a strain deleted for ORF73 and a revertant strain. Deletion of BoHV-4 ORF73 did not affect the capacity of the virus to replicate in vitro, but it prevented latent infection in vivo using a rabbit model. Interestingly, the strain deleted for ORF73 induced an anti-BoHV-4 humoral immune response comparable to that elicited by wild-type and revertant recombinants. Together, these results demonstrate that despite its relatively small size, BoHV-4 ORF73 is a functional homologue of larger rhadinovirus ORF73 orthologues, and highlight the potential of ORF73 deletion for the development of BoHV-4 as a vector in vaccinology. [less ▲]

Detailed reference viewed: 73 (40 ULg)
Peer Reviewed
See detailComparative study of Murid gammaherpesvirus 4 infection in mice and in its natural host, the bank voles.
François, Sylvie ULg; Vidick, Sarah ULg; Koteja, Pawel et al

Poster (2009, December 11)

Gammaherpesviruses are the archetypes of persistent viruses that have been identified in a range of animals from mice to man. They are host-range specific and establish persistent, productive infections ... [more ▼]

Gammaherpesviruses are the archetypes of persistent viruses that have been identified in a range of animals from mice to man. They are host-range specific and establish persistent, productive infections of immunocompetent hosts. Thus, infected individuals simultaneously both elicit antiviral protective immune response and secrete infectious virions. The best studied gammaherpesviruses are Human herpesvirus 4 and Human herpesvirus 8. As these viruses have no well-established in vivo infection model, related animal gammaherpesviruses are an important source of information. We are studying Murid herpesvirus 4 (MuHV-4), a virus that has originally been isolated from bank voles (Myodes glareolus). Although MuHV-4 has not been isolated from house mice (Mus musculus), infection of inbred laboratory mouse strains is commonly accepted as a good model for studying gammaherpesviruses in vivo. It has however never been possible to monitor viral reexcretion and virus transmission in this species suggesting that this model could be imperfect. In this study, we therefore characterized MuHV-4 infection in its natural host, the bank voles, through classical virological methods but also through global luciferase imaging for an anatomical complete view of the infection. Results obtained show that, after intra-nasal infection, the natural route of infection is similar in mice and voles. Following nasal productive infection, the virus spreads to the lung where the infection is accompanied by massive cellular infiltrates. By opposition to extensive viral replication observed in mice, the different analyses indicated that the viral replication was ~1000 fold lower in bank voles. This lower replication did however not affect colonization of latency sites in superficial cervical lymph nodes and spleen as measured by real-time PCR quantification of viral genomes in these organs. In conclusion, this study revealed that MuHV-4 can experimentally infect bank voles, the supposed natural host, but with a lower replicative power. As, gammaherpesvirus epidemiology indicates that transmission correlates with the latent load, our results suggest that gammaherpesviruses may have evolved to infect their hosts without extensive lytic spread. In the future, establishment of experimental transmission in a population of Myodes glareolus should help us to better understand mechanisms used by gammaherpesviruses to evade immune response. [less ▲]

Detailed reference viewed: 12 (5 ULg)
Peer Reviewed
See detailEx vivo bioluminescent detection of alcelaphine herpesvirus 1 infection during malignant catarrhal fever induced in rabbits
Dewals, Benjamin G ULg; Myster, Françoise ULg; Massart, François et al

Poster (2009, December 11)

Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla ... [more ▼]

Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be reproduced in rabbits. The lesions observed are very similar to those described in natural host species. Recently, we demonstrated that WD-MCF induced by AlHV-1 in rabbits is associated with the proliferation of CD8+ cells supporting a latent type of infection. In the present study, we investigated whether the virus could be detected ex vivo in the tissues of rabbits developing WD-MCF. Taking advantage of the recent cloning of the AlHV-1 genome as a bacterial artificial chromosome (BAC), we produced a recombinant plasmid encoding a firefly luciferase (LUC) expression cassette inserted in a non-coding region of the AlHV-1 genome. In vitro, the reconstituted AlHV-1 LUC strain replicated comparably to the parental strain in permissive cells and was able to induce a bioluminescent signal. In vivo, rabbits infected with the AlHV-1 LUC strain developed WD-MCF similarly to the parental wild-type strain with hyperthermia, increased CD8/CD4 ratio and viral genomic charge over time in PBMC and in lymph nodes at time of death. To identify the presence of AlHV-1 infection ex vivo, various organs of infected rabbits developing WD-MCF were analysed by bioluminescent imaging. Luciferase activity could be detected macroscopically at the time of death in most of analyzed organs including lung, popliteal and mesenteric lymph nodes, spleen, liver, kidney and appendix. Infectious virus could be isolated following co-cultures of lymph node and permissive cells, and the isolated virus retained the ability to induce a bioluminescent signal. In conclusion, we produced an AlHV-1 LUC recombinant and we were able to detect the AlHV-1 infection ex vivo in many organs at the time of death. [less ▲]

Detailed reference viewed: 51 (25 ULg)
Peer Reviewed
See detailMalignant catarrhal fever induced by alcelaphine herpesvirus 1 is associated with proliferation of CD8+ T cells supporting a latent infection
Dewals, Benjamin G ULg; Boudry, Christel; Farnir, Frédéric ULg et al

Poster (2009, September 11)

Alcelaphine herpesvirus 1 (AlHV 1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD MCF) when cross species transmitted to a variety of susceptible species of the Artiodactyla ... [more ▼]

Alcelaphine herpesvirus 1 (AlHV 1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD MCF) when cross species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-2’-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days post-inoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection. [less ▲]

Detailed reference viewed: 21 (10 ULg)
Peer Reviewed
See detailMalignant catarrhal fever induced by alcelaphine herpesvirus 1 is associated with proliferation of CD8+ T cells supporting a latent infection
Dewals, Benjamin G ULg; Boudry, Christel; Farnir, Frédéric ULg et al

Conference (2009, April)

Alcelaphine herpesvirus 1 (AlHV 1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD MCF) when cross species transmitted to a variety of susceptible species of the Artiodactyla ... [more ▼]

Alcelaphine herpesvirus 1 (AlHV 1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD MCF) when cross species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-2’-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days post-inoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection. [less ▲]

Detailed reference viewed: 21 (4 ULg)
Full Text
Peer Reviewed
See detailSubversion of complement by hematophagous parasites
SCHROEDER, Hélène ULg; SKELLY, PJ; ZIPFEL, PF et al

in Developmental & Comparative Immunology (2009), 33(1), 5-13

The complement system is a crucial part of innate and adaptive immunity which exerts a significant evolutionary pressure on pathogens. It has selected for those pathogens, mainly microorganisms but also ... [more ▼]

The complement system is a crucial part of innate and adaptive immunity which exerts a significant evolutionary pressure on pathogens. It has selected for those pathogens, mainly microorganisms but also parasites, that have evolved countermeasures. The characterization of how pathogens evade complement attack is a rapidly developing field of current research. In recent years, multiple complement evasion strategies have been characterized. In this review, we focus on complement escape mechanisms expressed by hematophagous parasites, a heterogeneous group of metazoan parasites that share the property of ingesting the whole blood of their host. Complement inhibition is crucial for parasite survival within the host tissue or to facilitate blood feeding. Finally, complement inhibition by hematophagous parasites may also contribute to their success as pathogen vectors. [less ▲]

Detailed reference viewed: 25 (12 ULg)
Full Text
Peer Reviewed
See detailA crucial role forlung interstitial macrophages in preventing airway allergy
Bedoret, Denis; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Short book of the Annual Congress of the European Respiratory Society (ERS), Vienne (2009)

Detailed reference viewed: 38 (14 ULg)
Peer Reviewed
See detailLung interstitial macrophages prevent the development of respiratory allergy
Bedoret, D.; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Proceedings of The Keystone Symposia: Allergy and Asthma. Keystone, Colorado, USA (2009)

Detailed reference viewed: 58 (20 ULg)
Full Text
Peer Reviewed
See detailClinical, virological, and immunological parameters associated with superinfection of latently with FeHV-1 infected cats
Richter, M.; Schudel, L.; Tobler, K. et al

in Veterinary Microbiology (2009)

Detailed reference viewed: 30 (7 ULg)
Full Text
Peer Reviewed
See detailThe major portal of entry of koi herpesvirus in cyprinus carpio is the skin.
Costes, Bérénice ULg; Stalin Raj, V.; Michel, Benjamin ULg et al

in Journal of Virology (2009)

Koi herpesvirus (KHV), recently designated in the species Cyprinid Herpesvirus 3, is the causative agent of a lethal disease in koi and common carp. In the present study, we investigated the portal of ... [more ▼]

Koi herpesvirus (KHV), recently designated in the species Cyprinid Herpesvirus 3, is the causative agent of a lethal disease in koi and common carp. In the present study, we investigated the portal of entry of KHV in carp using bioluminescence imaging. Taking profit of the recent cloning of the KHV genome as a bacterial artificial chromosome (BAC), we produced a recombinant plasmid encoding a firefly luciferase (LUC) expression cassette inserted in the intergenic region between ORF 136 and ORF 137. Two viral strains were then reconstituted from the modified plasmid: the FL BAC 136 LUC excised strain and the FL BAC 136 LUC TK revertant strain encoding a disrupted and a wild-type thymidine kinase (TK) locus, respectively. In vitro, the two recombinant strains replicated comparably to the parental FL strain. The FL BAC 136 LUC TK revertant strain was shown in vitro to induce a bioluminescent signal allowing the detection of single positive cells as early as 24 hours post-infection; while in vivo, it induced KHV infection in carp that was indistinguishable from that induced by the parental FL strain. To identify the KHV portal of entry, carp were analyzed by bioluminescence imaging at different time post-infection with the FL BAC 136 LUC TK revertant strain. These analyses demonstrated that the skin of the fish, covering the fins and also the body, is the major portal of entry of KHV in carp. Finally, to further demonstrate the role of the skin as the KHV portal of entry, we constructed an original system nicknamed "U-tube" to perform per-cutaneous infection restricted to the posterior part of the fish. All the data obtained in the present study demonstrate that the skin and not the gills is the major portal of entry of KHV in carp. [less ▲]

Detailed reference viewed: 61 (11 ULg)
Peer Reviewed
See detailInterstitial macrophages are essential for maintaining immune homeostasis in the lung
Bedoret, Denis; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Proceedings of The Allergy & Asthma Symposium: Bridging Innate and Adaptive Immunity (2009)

Detailed reference viewed: 56 (26 ULg)
Full Text
Peer Reviewed
See detailLung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice
Bedoret, Denis ULg; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Journal of Clinical Investigation (2009), 119(12), 3723-38

The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC ... [more ▼]

The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC-driven Th2 cell response to harmless inhaled antigens, thereby promoting allergic asthma. However, only a small fraction of people exposed to environmental LPS develop allergic asthma. What prevents most people from mounting a lung DC-driven Th2 response upon exposure to LPS is not understood. Here we have shown that lung interstitial macrophages (IMs), a cell population with no previously described in vivo function, prevent induction of a Th2 response in mice challenged with LPS and an experimental harmless airborne antigen. IMs, but not alveolar macrophages, were found to produce high levels of IL-10 and to inhibit LPS-induced maturation and migration of DCs loaded with the experimental harmless airborne antigen in an IL-10-dependent manner. We further demonstrated that specific in vivo elimination of IMs led to overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS. This study has revealed a crucial role for IMs in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that although airborne LPS has the ability to promote the induction of Th2 responses by lung DCs, it does not provoke airway allergy under normal conditions. [less ▲]

Detailed reference viewed: 195 (71 ULg)
Full Text
Peer Reviewed
See detailCo-infection with two closely related alphaherpesviruses results in a highly diversified recombination mosaic displaying negative genetic interference
Muylkens, Benoît ULg; Farnir, Frédéric ULg; Meurens, François et al

in Journal of Virology (2009), 83(7), 3127-3137

Phylogenetic studies of the emergence and spread of natural recombinants in herpesviruses infecting humans and animals have been reported recently. However, despite an ever-increasing amount of evidence ... [more ▼]

Phylogenetic studies of the emergence and spread of natural recombinants in herpesviruses infecting humans and animals have been reported recently. However, despite an ever-increasing amount of evidence of recombination in herpesvirus history, the recombination process and the consequences on the genetic diversity of the progeny remain poorly characterized. We addressed this issue by using multiple single-nucleotide polymorphisms (SNPs) differentiating the two subtypes of an alphaherpesvirus, bovine herpesvirus 1 (BoHV-1). Analysis of a large sample of progeny virions obtained in a single growth cycle of coinfected BoHV-1 strains provided a prospective investigation of the recombination dynamics by using SNPs as recombination markers. We found that the simultaneous infection with two closely related herpesviruses results in a highly diversified recombination mosaic. From the analysis of multiple recombinants arising in the progeny, we provide the first evidence of genetic interference influencing the recombination process in herpesviruses. In addition, we report striking differences in the levels of recombination frequency observed along the BoHV-1 genome. With particular emphasis on the genetic structure of a progeny virus population rising in vitro, our data show to which extent recombination participates to the genetic diversification of herpesviruses [less ▲]

Detailed reference viewed: 80 (27 ULg)