References of "Vanderplasschen, Alain"
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See detailAnalyse détaillée de la seconde version de l’avant-projet de Code du bien-être animal wallon. Lecture commentée au 21/03/2018 du Chapitre 8 (Expérimentation animale)
Drion, Pierre ULiege; Corhay, Albert ULiege; Haubruge, Eric ULiege et al

Report (2018)

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par ... [more ▼]

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par les décrets du Gouvernement wallon). Certains éléments sont repris tels quels de la Directive 2010/63. Cela est nécessaire car la Directive européenne en tant que telle n’a pas de force obligatoire en Belgique. Elle doit être transcrite par un instrument législatif (avant, la Loi de 1984 et ses modifications, aujourd’hui, le projet de code pour la Région wallonne). Certains aspects semblent flous, mais renvoient à des dispositions que le Gouvernement doit encore prendre (au travers d’arrêtés du Gouvernement wallon, comme le faisaient avant les nombreux arrêtés royaux et du gouvernement qui réglementent la matière). Les arrêtés d’exécution devront obligatoirement tenir compte de la Directive européenne et s’inspirer de dispositions actuellement en vigueur. [less ▲]

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See detailBiocontrol of invasive carp : risks abound
Marshall, J; Davison, A. J.; Kopf, R. K. et al

in Science (2018)

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See detailL’expérimentation animale reste indispensable (OPINION)
Amorim, Christiani; Andris, Fabienne; Arckens, Lut et al

Article for general public (2017)

Trop fréquemment, l’expérimentation animale est présentée comme une pratique archaïque. Elle a bien changé. Et 100 % des patients traités le sont grâce aux concepts et techniques développés grâce à elle.

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See detailIL-4Ra-dependent macrophage responses in the liver during murine schistosomiasis
Rolot, Marion ULiege; Dougall, Annette; Gillet, Laurent et al

Poster (2017, September)

During Schistosoma mansoni infection in mice, IL-4 receptor-dependent alternatively activated macrophages (aaMφ) response mediate host protection. Here, we used LysMcreIl4ra−/lox mice to determine whether ... [more ▼]

During Schistosoma mansoni infection in mice, IL-4 receptor-dependent alternatively activated macrophages (aaMφ) response mediate host protection. Here, we used LysMcreIl4ra−/lox mice to determine whether the absence of Mφ-specific IL-4 receptor signalling modifies the dynamics of Mφ responses in liver granulomas after S. mansoni infection. Liver inflammatory response was investigated after low-dose S. mansoni infection. We observed significantly increased total leukocyte numbers in the liver by week 8 in LysMcreIl4ra−/lox mice while mice survived the infection similarly to littermate controls. Over the course of infection, we observed that CD11blowMerTK+CD64+ resident Küpffer cells (KCs) were severely reducing in term of numbers independently of IL-4Rα signalling. While KCs lowered, Ly6Chi monocytes were recruited in the liver from 6 weeks pi, proliferate strongly at week 8 and acquire CD64 expression. The number of Ly6Chi recruited monocytes were significantly higher in LysMcreIl4ra−/lox mice than littermate controls. From 8 weeks pi, CD11blow KCs seemed to be replaced by CD11bhighMerTK+CD64+F4/80+ Mφ, probably derived from recruited Ly6Chi monocytes. At week 8 pi, expression of Ym1 and Relm-alpha was significantly reduced in hepatic CD11bhigh Mφ of LysMcreIl4ra−/lox mice compared to littermate controls. These results suggest that recruited monocytes differentiate into Mφ at the cost of resident KCs independently of IL-4Rα and validate the use of LysMcreIl4ra−/lox mice to study IL-4Rα-dependent activation of monocyte-derived granuloma Mφ during schistosomiasis. [less ▲]

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See detailProteomic and functional analyses of the virion transmembrane proteome of cyprinid herpesvirus 3.
Vancsok, Catherine ULiege; Penaranda, Ma Michelle D.; Raj, V. Stalin et al

in Journal of Virology (2017), 91(21),

Virion transmembrane proteins (VTPs) mediate key functions in the herpesvirus infectious cycle. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses. The present study was devoted to ... [more ▼]

Virion transmembrane proteins (VTPs) mediate key functions in the herpesvirus infectious cycle. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses. The present study was devoted to CyHV-3 VTPs. Using mass spectrometry approaches, we identified 16 VTPs of the CyHV-3 FL strain. Mutagenesis experiments demonstrated that eight of these proteins are essential for viral growth in vitro (ORF32, ORF59, ORF81, ORF83, ORF99, ORF106, ORF115, and ORF131), and eight are non-essential (ORF25, ORF64, ORF65, ORF108, ORF132, ORF136, ORF148, and ORF149). Among the non-essential proteins, deletion of ORF25, ORF132, ORF136, ORF148, or ORF149 affects viral replication in vitro, and deletion of ORF25, ORF64, ORF108, ORF132, or ORF149 impacts plaque size. Lack of ORF148 or ORF25 causes attenuation in vivo to a minor or major extent, respectively. The safety and efficacy of a virus lacking ORF25 were compared to those of a previously described vaccine candidate deleted for ORF56 and ORF57 (Delta56-57). Using quantitative PCR, we demonstrated that the ORF25 deleted virus infects fish through skin infection and then spreads to internal organs as reported previously for the wild-type parental virus and the Delta56-57 virus. However, compared to the parental wild-type virus, the replication of the ORF25 deleted virus was reduced in intensity and duration to levels similar to those observed for the Delta56-57 virus. Vaccination of fish with a virus lacking ORF25 was safe but had low efficacy at the doses tested. This characterization of the virion transmembrane proteome of CyHV-3 provides a firm basis for further research on alloherpesvirus VTPs.IMPORTANCE Virion transmembrane proteins play key roles in the biology of herpesviruses. Cyprinid herpesvirus 3 (CyHV-3) is the archetype of fish alloherpesviruses and the causative agent of major economic losses in common and koi carp worldwide. In this study of the virion transmembrane proteome of CyHV-3, the major findings were: (i) the FL strain encodes 16 virion transmembrane proteins; (ii) eight of these proteins are essential for viral growth in vitro; (iii) seven of the non-essential proteins affect viral growth in vitro, and two affect virulence in vivo; and (iv) a mutant lacking ORF25 is highly attenuated but induces moderate immune protection. This study represents a major breakthrough in understanding the biology of CyHV-3 and will contribute to the development of prophylactic methods. It also provides a firm basis for the further research on alloherpesvirus virion transmembrane proteins. [less ▲]

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See detailCyprinid Herpesvirus 3 ORF57 is an essential virulence factor
Boutier, Maxime ULiege; Gao, Yuan; Vancsok, Catherine et al

Poster (2017)

The genus Cyprinivirus comprises phylogenetically related viruses causing important economic losses in aquaculture. Its archetype species, the cyprinid herpesvirus 3 (CyHV 3) is the causative agent of ... [more ▼]

The genus Cyprinivirus comprises phylogenetically related viruses causing important economic losses in aquaculture. Its archetype species, the cyprinid herpesvirus 3 (CyHV 3) is the causative agent of mass mortalities in koi and common carp worldwide. Recently, we reported the development of a recombinant attenuated vaccine against CyHV 3 for mass vaccination of carp. This attenuated vaccine encodes a deletion encompassing ORF56 and ORF57. In the present study, we investigated the relative contribution of ORF56 and ORF57 in the safety observed for the ORF56-57 double deleted genotype. Single deleted recombinants were produced based on deletion-insertion of a galK cassette, inserting stop codons in frame with the sequence upstream of the deletion and disrupting the frame of the remaining sequence downstream of the deletion. Inoculation of these recombinants to carp demonstrated that the absence of ORF56 protein expression did not affect virulence; while ORF57 deletion led to an attenuation comparable to the one observed for the ORF56-57 deletion. To further demonstrate the role of ORF57 as a key virulence factor, a recombinant unable to express ORF57 protein was produced by insertion of multiple stop codons in the ORF. In vivo testing of this recombinant revealed a safety-efficacy profile comparable to the one observed for the vaccine candidate deleted for ORF56 and ORF57. Altogether, the present study demonstrates the role of ORF57 as a key virulence factor of CyHV 3 and identifies ORF57 orthologues encoded by other pathogenic cypriniviruses as gene candidates for production of attenuated recombinant vaccines. [less ▲]

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See detailA gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes.
Machiels, Bénédicte ULiege; Dourcy, Mickael ULiege; Xiao, Xue ULiege et al

in Nature Immunology (2017)

The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we ... [more ▼]

The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we investigated how infection with a gammaherpesvirus affected the subsequent development of allergic asthma. We found that murid herpesvirus 4 (MuHV-4) inhibited the development of house dust mite (HDM)-induced experimental asthma by modulating lung innate immune cells. Specifically, infection with MuHV-4 caused the replacement of resident alveolar macrophages (AMs) by monocytes with regulatory functions. Monocyte-derived AMs blocked the ability of dendritic cells to trigger a HDM-specific response by the TH2 subset of helper T cells. Our results indicate that replacement of embryonic AMs by regulatory monocytes is a major mechanism underlying the long-term training of lung immunity after infection. [less ▲]

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See detailIdentification of an essential virulence gene of cyprinid herpesvirus 3.
Boutier, Maxime ULiege; Gao, Yuan; Vancsok, Catherine ULiege et al

in Antiviral Research (2017), 145

The genus Cyprinivirus consists of a growing list of phylogenetically related viruses, some of which cause severe economic losses to the aquaculture industry. The archetypal member, cyprinid herpesvirus 3 ... [more ▼]

The genus Cyprinivirus consists of a growing list of phylogenetically related viruses, some of which cause severe economic losses to the aquaculture industry. The archetypal member, cyprinid herpesvirus 3 (CyHV-3) causes mass mortalities worldwide in koi and common carp. A CyHV-3 mutant was described previously that is attenuated in vivo by a deletion affecting two genes (ORF56 and ORF57). The relative contributions of ORF56 and ORF57 to the safety and efficacy profile of this vaccine candidate have now been assessed by analysing viruses individually deleted for ORF56 or ORF57. Inoculation of these viruses into carp demonstrated that the absence of ORF56 did not affect virulence, whereas the absence of ORF57 led to an attenuation comparable to, though slightly less than, that of the doubly deleted virus. To demonstrate further the role of ORF57 as a key virulence factor, a mutant retaining the ORF57 region but unable to express the ORF57 protein was produced by inserting multiple in-frame stop codons into the coding region. Analysis of this virus in vivo revealed a safety and efficacy profile comparable to that of the doubly deleted virus. These findings show that ORF57 encodes an essential CyHV-3 virulence factor. They also indicate that ORF57 orthologues in other cypriniviruses may offer promising targets for the rational design of attenuated recombinant vaccines. [less ▲]

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See detailThe Major Envelope Glycoprotein of Murid Herpesvirus 4 Promotes Sexual Transmission.
Zeippen, Caroline ULiege; Javaux, Justine; Xiao, Xue ULiege et al

in Journal of Virology (2017), 91(13),

Gammaherpesviruses are important human and animal pathogens. Infection control has proven difficult because the key process of transmission is ill understood. Murid herpesvirus 4 (MuHV-4), a ... [more ▼]

Gammaherpesviruses are important human and animal pathogens. Infection control has proven difficult because the key process of transmission is ill understood. Murid herpesvirus 4 (MuHV-4), a gammaherpesvirus of mice, is transmitted sexually. We show that this depends on the major virion envelope glycoprotein gp150. gp150 is redundant for host entry, and in vitro, it regulates rather than promotes cell binding. We show that gp150-deficient MuHV-4 reaches and replicates normally in the female genital tract after nasal infection but is poorly released from vaginal epithelial cells and fails to pass from the female to the male genital tract during sexual contact. Thus, we show that the regulation of virion binding is a key component of spontaneous gammaherpesvirus transmission.IMPORTANCE Gammaherpesviruses are responsible for many important diseases in both animals and humans. Some important aspects of their life cycle are still poorly understood. Key among these is viral transmission. Here we show that the major envelope glycoprotein of murid herpesvirus 4 functions not in entry or dissemination but in virion release to allow sexual transmission to new hosts. [less ▲]

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See detailConserved Fever Pathways across Vertebrates: A Herpesvirus Expressed Decoy TNF-alpha Receptor Delays Behavioral Fever in Fish.
Rakus, Krzysztof; Ronsmans, Maygane; Forlenza, Maria et al

in Cell Host & Microbe (2017), 21(2), 244-253

Both endotherms and ectotherms (e.g., fish) increase their body temperature to limit pathogen infection. Ectotherms do so by moving to warmer places, hence the term "behavioral fever." We studied the ... [more ▼]

Both endotherms and ectotherms (e.g., fish) increase their body temperature to limit pathogen infection. Ectotherms do so by moving to warmer places, hence the term "behavioral fever." We studied the manifestation of behavioral fever in the common carp infected by cyprinid herpesvirus 3, a native carp pathogen. Carp maintained at 24 degrees C died from the infection, whereas those housed in multi-chamber tanks encompassing a 24 degrees C-32 degrees C gradient migrated transiently to the warmest compartment and survived as a consequence. Behavioral fever manifested only at advanced stages of infection. Consistent with this, expression of CyHV-3 ORF12, encoding a soluble decoy receptor for TNF-alpha, delayed the manifestation of behavioral fever and promoted CyHV-3 replication in the context of a temperature gradient. Injection of anti-TNF-alpha neutralizing antibodies suppressed behavioral fever, and decreased fish survival in response to infection. This study provides a unique example of how viruses have evolved to alter host behavior to increase fitness. [less ▲]

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See detailBehavioral fever in ectothermic vertebrates.
Rakus, Krzysztof; Ronsmans, Maygane; Vanderplasschen, Alain ULiege

in Developmental & Comparative Immunology (2017), 66

Fever is an evolutionary conserved defense mechanism which is present in both endothermic and ectothermic vertebrates. Ectotherms in response to infection can increase their body temperature by moving to ... [more ▼]

Fever is an evolutionary conserved defense mechanism which is present in both endothermic and ectothermic vertebrates. Ectotherms in response to infection can increase their body temperature by moving to warmer places. This process is known as behavioral fever. In this review, we summarize the current knowledge on the mechanisms of induction of fever in mammals. We further discuss the evolutionary conserved mechanisms existing between fever of mammals and behavioral fever of ectothermic vertebrates. Finally, the experimental evidences supporting an adaptive value of behavioral fever expressed by ectothermic vertebrates are summarized. [less ▲]

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See detailViral glycoprotein gp150 promotes sexual transmission of Murid Herpesvirus-4
Zeippen, Caroline ULiege; Javaux, Justine ULiege; Xiao, Xue ULiege et al

Poster (2016, November 28)

Gammaherpesviruses are important pathogens in human and veterinary medicine. During co-evolution with their hosts, they developed many strategies allowing them to shed infectious particles in presence of ... [more ▼]

Gammaherpesviruses are important pathogens in human and veterinary medicine. During co-evolution with their hosts, they developed many strategies allowing them to shed infectious particles in presence of immune response. Understanding these strategies is likely to be important to control infection. Interestingly, we recently observed that Murid herpesvirus 4 (MuHV-4), a gammaherpesvirus infecting laboratory mice, could be sexually transmitted between mice. This model offers therefore the opportunity to understand the mechanisms underlying natural transmission. Some of these mechanisms could rely on the glycoprotein 150 (gp150), which could limit virus neutralization and promote the release of infectious particles from cells. In this study, we tested therefore the importance of gp150 in the context of MuHV-4 sexual transmission. Briefly, female mice were infected with WT or gp150- strains expressing luciferase. They were imaged with an in vivo imaging system to follow infection. When lytic replication was observed in the genital tract, infected females were mated with naïve males to compare the capacity of transmission of the two strains. Our results show that, while the gp150- strain has no deficit in reaching and replicating in the female genital tract, it displays a major deficit of sexual transmission in comparison with WT virions. Interestingly, this deficit appears to reflect a deficit of virions release from vaginal epithelial cells. Altogether, our results show that, while gp150 is not required for efficient dissemination and maintenance of MuHV-4 within its host, it is essential for efficient transmission, by promoting the releasing of infectious particles from the mucosal cells. [less ▲]

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