References of "Vanderplasschen, Alain"
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See detailThe replication characteristics of infectious laryngotracheitis virus (ILTV) in the respiratory and conjunctival mucosa
Reddy, V.R.; Steukers, L.; Li, Y. et al

in Avian Pathology : Journal of the W.V.P.A (2014), 21

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See detailThe A2 gene of alcelaphine herpesvirus-1 is a transcriptional regulator affecting cytotoxicity in virus-infected T cells but is not required for malignant catarrhal fever induction in rabbits.
Parameswaran, Nevi; Dewals, Benjamin G ULg; Giles, Tom C. et al

in Virus research (2014)

Alcelaphine herpesvirus-1 (AlHV-1) causes malignant catarrhal fever (MCF). The A2 gene of AlHV-1 is a member of the bZIP transcription factor family. We wished to determine whether A2 is a virulence gene ... [more ▼]

Alcelaphine herpesvirus-1 (AlHV-1) causes malignant catarrhal fever (MCF). The A2 gene of AlHV-1 is a member of the bZIP transcription factor family. We wished to determine whether A2 is a virulence gene or not and whether it is involved in pathogenesis by interference with host transcription pathways. An A2 gene knockout (A2DeltaAlHV-1) virus, revertant (A2revAlHV-1) virus, and wild-type virus (wtAlHV-1) were used to infect three groups of rabbits. A2DeltaAlHV-1-infected rabbits succumbed to MCF, albeit with a delayed onset compared to the control groups, so A2 is not a critical virulence factor. Differential gene transcription analysis by RNAseq and qRT-PCR validation of a selection of these was performed in infected large granular lymphocyte (LGL) T cells obtained in culture from the MCF-affected animals. A2 was involved in the transcriptional regulation of immunological, cell cycle and apoptosis pathways. In particular, there was a bias towards gammadelta T cell receptor (TCR) expression and downregulation of alphabeta TCR. TCR signalling, apoptosis, cell cycle, IFN-gamma and NFAT pathways were affected. Of particular interest was partial inhibition of the cytotoxicity-associated pathways involving perforin and the granzymes A and B in the A2DeltaAlHV-1-infected LGLs compared to controls. In functional assays, A2DeltaAlHV-1-infected LGLs were significantly less cytotoxic than wtAlHV-1- and A2revAlHV-1-infected LGLs using rabbit corneal epithelial cells (SIRC) as targets. This implies that A2 is involved in a pathway enhancing the expression of LGL cytotoxicity. This is important as virus-infected T cell cytotoxicity in vivo has been suggested as a potential mechanism of disease induction in MCF. [less ▲]

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See detailThe IL-10 homologue encoded by cyprinid herpesvirus 3 is essential neither for viral replication in vitro nor for virulence in vivo
Ouyang, Ping ULg; Rakus, Krzysztof ULg; Boutier, Maxime ULg et al

in Veterinary Research (2013)

Cyprinid herpesvirus 3 (CyHV-3), a member of the family Alloherpesviridae, is the causative agent of a lethal disease in common and koi carp. CyHV-3 ORF134 encodes an interleukin-10 (IL-10) homologue. The ... [more ▼]

Cyprinid herpesvirus 3 (CyHV-3), a member of the family Alloherpesviridae, is the causative agent of a lethal disease in common and koi carp. CyHV-3 ORF134 encodes an interleukin-10 (IL-10) homologue. The present study was devoted to this ORF. Transcriptomic analyses revealed that ORF134 is expressed as a spliced gene belonging to the early-late class. Proteomic analyses of CyHV-3 infected cell supernatant demonstrated that the ORF134 expression product is one of the most abundant proteins of the CyHV-3 secretome. To investigate the role of ORF134 in viral replication in vitro and in virulence in vivo, a deleted strain and a derived revertant strain were produced using BAC cloning technologies. The recombinant ORF134 deleted strain replicated in vitro comparably to the parental and the revertant strains. Infection of fish by immersion in water containing the virus induced comparable CyHV-3 disease for the three virus genotypes tested (wild type, deleted and revertant). Quantification of viral DNA by real time TaqMan PCR (in the gills and the kidney) and analysis of carp cytokine expression (in the spleen) by RT-qPCR at different times post-infection did not revealed any significant difference between the groups of fish infected with the three virus genotypes. Similarly, histological examination of the gills and the kidney of infected fish revealed no significant differences between fish infected with ORF134 deleted virus versus fish infected with the control parental or revertant strains. All together, the results of the present study demonstrate that the IL-10 homologue encoded by CyHV-3 is essential neither for viral replication in vitro nor for virulence in common carp. [less ▲]

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See detailAn essential role for gamma-herpesvirus latency-associated nuclear antigen homolog in an acute lymphoproliferative disease of cattle.
Palmeira, Leonor; Sorel, Océane ULg; Van Campe, Willem et al

in Proceedings of the National Academy of Sciences of the United States of America (2013)

Wildebeests carry asymptomatically alcelaphine herpesvirus 1 (AlHV-1), a gamma-herpesvirus inducing malignant catarrhal fever (MCF) to several ruminant species (including cattle). This acute and lethal ... [more ▼]

Wildebeests carry asymptomatically alcelaphine herpesvirus 1 (AlHV-1), a gamma-herpesvirus inducing malignant catarrhal fever (MCF) to several ruminant species (including cattle). This acute and lethal lymphoproliferative disease occurs after a prolonged asymptomatic incubation period after transmission. Our recent findings with the rabbit model indicated that AlHV-1 infection is not productive during MCF. Here, we investigated whether latency establishment could explain this apparent absence of productive infection and sought to determine its role in MCF pathogenesis. First, whole-genome cellular and viral gene expression analyses were performed in lymph nodes of MCF-developing calves. Whereas a severe disruption in cellular genes was observed, only 10% of the entire AlHV-1 genome was expressed, contrasting with the 45% observed during productive infection in vitro. In vivo, the expressed viral genes included the latency-associated nuclear antigen homolog ORF73 but none of the regions known to be essential for productive infection. Next, genomic conformation analyses revealed that AlHV-1 was essentially episomal, further suggesting that MCF might be the consequence of a latent infection rather than abortive lytic infection. This hypothesis was further supported by the high frequencies of infected CD8+ T cells during MCF using immunodetection of ORF73 protein and single-cell RT-PCR approaches. Finally, the role of latency-associated ORF73 was addressed. A lack of ORF73 did not impair initial virus replication in vivo, but it rendered AlHV-1 unable to induce MCF and persist in vivo and conferred protection against a lethal challenge with a WT virus. Together, these findings suggest that a latent infection is essential for MCF induction. [less ▲]

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See detailIN-VITRO EVALUATION OF A-5021 ANTI-VIRAL ACTIVITY AGAINST TESTUDINID HERPESVIRUS 3 AND INITIAL PHARMACOKINETIC STUDY IN HERMANN'S TORTOISE (Testudo hermanni)
Gandar, Frederic ULg; Vrancken, Robert; Diez, Marianne ULg et al

Conference (2013, April 23)

Testudinid herpesvirus infections in tortoises belonging to the Testudinidae family are well known for decades, but their pathogenesis remains poorly understood and treatments are often empirical. This ... [more ▼]

Testudinid herpesvirus infections in tortoises belonging to the Testudinidae family are well known for decades, but their pathogenesis remains poorly understood and treatments are often empirical. This study describes the in vitro evaluation of selected anti-herpesvirus compounds against Testudinid Herpesvirus 3 (THV-3). A-5021, a compound with known broad-spectrum anti-herpetic activity, showed to be 9 times more potent than acyclovir, with an EC50 of 13.2 µM and inducing a complete inhibition of viral replication at 37.7 µM. Initial pharmacokinetic parameters were determined after a single sub-cutaneous administration of 5 and 10 mg/kg in Hermann’s tortoises (Testudo hermanni, n=3). Blood samples were collected at different time points and plasma concentrations of A-5021 were determined. No adverse effects were clinically observed and plasma concentrations remained above the EC50 for 2.8 and 4.2 h after administration of 5 and 10 mg/kg, respectively. These preliminary data provide a basis for further proof-of-concept studies for a potential prophylactic or therapeutic treatment of THV-3 infection in tortoises [less ▲]

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See detailCis-acting inhibition of MHC class I-restricted epitope presentation by Alcelaphine herpesvirus 1 genome maintenance protein
Sorel, Océane ULg; Myster, Françoise ULg; Vanderplasschen, Alain ULg et al

Poster (2013, January 18)

γ-Herpesviruses persist as latent episomes in actively dividing lymphocytes. Their consequent need to express a viral genome maintenance protein (GMP) during latency presents a potential immune target ... [more ▼]

γ-Herpesviruses persist as latent episomes in actively dividing lymphocytes. Their consequent need to express a viral genome maintenance protein (GMP) during latency presents a potential immune target. However, the GMPs from several γ-herpesviruses have evolved related strategies to limit their own MHC class I epitope presentation to cytotoxic T lymphocytes (CTLs). Alcelaphine herpesvirus 1 (AlHV-1) is a γ-herpesvirus that persists asymptomatically in its natural host, the wildebeest. However, AlHV-1 transmission to a large number of susceptible ruminants, including cattle, results in the development of a lethal lymphoproliferative disease named malignant catarrhal fever (MCF). We recently observed that the AlHV-1 GMP-homologue encoded by ORF73 is highly expressed during MCF and that the impairment of its expression renders AlHV-1 unable to induce MCF. With its 1300 aa, AlHV-1 ORF73 is the largest γ-herpesvirus GMP described to date and contains a large acidic internal repeat region that could be involved in the cis-acting CTL evasion mechanism. Here, we sought to determine the CTL evasion properties of AlHV-1 ORF73. We first performed bioinformatic analyses to characterize the protein domains. Then, we used an in vitro assay to demonstrate that ORF73 severely limits the presentation at the cell surface of an MHC class I-restricted epitope linked to ORF73 in cis. These results suggest that AlHV-1 has developed mechanisms to evade cytotoxic anti-viral response during latency. The exact mechanisms explaining the presentation defect remain to be deciphered as well as the role of the cis-acting CTL evasion mechanism of ORF73 in the pathogenesis of MCF. [less ▲]

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See detailIllumination of murine gammaherpesvirus-68 cycle reveals a sexual transmission route from females to males in laboratory mice.
Francois, Sylvie; Vidick, Sarah ULg; Sarlet, Mickael et al

in PLoS Pathogens (2013), 9(4), 1003292

Transmission is a matter of life or death for pathogen lineages and can therefore be considered as the main motor of their evolution. Gammaherpesviruses are archetypal pathogenic persistent viruses which ... [more ▼]

Transmission is a matter of life or death for pathogen lineages and can therefore be considered as the main motor of their evolution. Gammaherpesviruses are archetypal pathogenic persistent viruses which have evolved to be transmitted in presence of specific immune response. Identifying their mode of transmission and their mechanisms of immune evasion is therefore essential to develop prophylactic and therapeutic strategies against these infections. As the known human gammaherpesviruses, Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus are host-specific and lack a convenient in vivo infection model; related animal gammaherpesviruses, such as murine gammaherpesvirus-68 (MHV-68), are commonly used as general models of gammaherpesvirus infections in vivo. To date, it has however never been possible to monitor viral excretion or virus transmission of MHV-68 in laboratory mice population. In this study, we have used MHV-68 associated with global luciferase imaging to investigate potential excretion sites of this virus in laboratory mice. This allowed us to identify a genital excretion site of MHV-68 following intranasal infection and latency establishment in female mice. This excretion occurred at the external border of the vagina and was dependent on the presence of estrogens. However, MHV-68 vaginal excretion was not associated with vertical transmission to the litter or with horizontal transmission to female mice. In contrast, we observed efficient virus transmission to naive males after sexual contact. In vivo imaging allowed us to show that MHV-68 firstly replicated in penis epithelium and corpus cavernosum before spreading to draining lymph nodes and spleen. All together, those results revealed the first experimental transmission model for MHV-68 in laboratory mice. In the future, this model could help us to better understand the biology of gammaherpesviruses and could also allow the development of strategies that could prevent the spread of these viruses in natural populations. [less ▲]

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See detailEffect of myeloperoxidase and anoxia/reoxygenation on mitochondrial respiratory function of cultured primary equine skeletal myoblasts.
Ceusters, Justine ULg; Mouithys-Mickalad, Ange ULg; Franck, Thierry ULg et al

in Mitochondrion (2013), 13(5),

Horses are particularly sensitive to excessive inflammatory reaction where myeloperoxidase, a marker of inflammation, may contribute to mitochondrial dysfunctions. This study investigated the interaction ... [more ▼]

Horses are particularly sensitive to excessive inflammatory reaction where myeloperoxidase, a marker of inflammation, may contribute to mitochondrial dysfunctions. This study investigated the interaction between myeloperoxidase and cultured primary equine skeletal myoblasts, particularly its effect on mitochondrial respiration combined or not with anoxia followed by reoxygenation (AR). We showed that active myeloperoxidase entered into the cells, interacted with mitochondria and decreased routine and maximal respirations. When combined with AR, myeloperoxidase caused a further decrease of these respiratory parameters while the leak increased. Our results indicate that myeloperoxidase amplifies the mitochondrial damages initiated by AR phenomenon and alters the mitochondrial function. [less ▲]

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See detailProteomic characterization of murid herpesvirus 4 extracellular virions.
Vidick, Sarah ULg; Leroy, Baptiste; Gonon Rodrigues Palmeira, Leonor ULg et al

in PloS one (2013), 8(12), 83842

Gammaherpesvirinae, such as the human Epstein-Barr virus (EBV) and the Kaposi's sarcoma associated herpesvirus (KSHV) are highly prevalent pathogens that have been associated with several neoplastic ... [more ▼]

Gammaherpesvirinae, such as the human Epstein-Barr virus (EBV) and the Kaposi's sarcoma associated herpesvirus (KSHV) are highly prevalent pathogens that have been associated with several neoplastic diseases. As EBV and KSHV are host-range specific and replicate poorly in vitro, animal counterparts such as Murid herpesvirus-4 (MuHV-4) have been widely used as models. In this study, we used MuHV-4 in order to improve the knowledge about proteins that compose gammaherpesviruses virions. To this end, MuHV-4 extracellular virions were isolated and structural proteins were identified using liquid chromatography tandem mass spectrometry-based proteomic approaches. These analyses allowed the identification of 31 structural proteins encoded by the MuHV-4 genome which were classified as capsid (8), envelope (9), tegument (13) and unclassified (1) structural proteins. In addition, we estimated the relative abundance of the identified proteins in MuHV-4 virions by using exponentially modified protein abundance index analyses. In parallel, several host proteins were found in purified MuHV-4 virions including Annexin A2. Although Annexin A2 has previously been detected in different virions from various families, its role in the virion remains controversial. Interestingly, despite its relatively high abundance in virions, Annexin A2 was not essential for the growth of MuHV-4 in vitro. Altogether, these results extend previous work aimed at determining the composition of gammaherpesvirus virions and provide novel insights for understanding MuHV-4 biology. [less ▲]

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See detailCyprinid herpesvirus 3 : an intersting virus for applied and fundamental research
Rakus; Ouyang, Ping; Boutier, Maxime ULg et al

in Veterinary Research (2013), 44

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See detailInterkeukin-10s encoded by viruses : a remarkable example of independent acquisitions of a cellular gene by viruses and its subsequent evolution in the viral genome
Ouyang, Ping; Rakus, Krzysztof ULg; Van Beurden, Steven et al

in Journal of General Virology (The) (2013)

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See detailLaboratory validation of a lateral flow device for the detection of CyHV-3 antigens in gill swabs
Vrancken, Robert; Boutier, Maxime ULg; Ronsmans, Maygane ULg et al

in Journal of Virological Methods (2013), 193

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See detailUse of Staby technology for development and production of DNA vaccines free of antibiotic resistance gene
Reschner; Scohy, S.; Vandermeulen, G. et al

in Human Vaccines (2013), 9

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See detailFeeding Cyprinus carpio with infectious materials mediates cyprinid herpesvirus 3 entry through infection of pharyngeal periodontal mucosa
Fournier, Guillaume ULg; Boutier, Maxime ULg; Victor, Stalin Raj et al

in Veterinary Research (2012), 43(6),

Cyprinid herpesvirus 3 (CyHV-3), also known as Koi herpesvirus, is the etiological agent of a mortal disease in common and koi carp. Recently, we investigated the entry of CyHV-3 in carp using ... [more ▼]

Cyprinid herpesvirus 3 (CyHV-3), also known as Koi herpesvirus, is the etiological agent of a mortal disease in common and koi carp. Recently, we investigated the entry of CyHV-3 in carp using bioluminescence imaging and a CyHV-3 recombinant strain expressing luciferase (LUC). We demonstrated that the skin is the major portal of entry after inoculation of carp by immersion in water containing CyHV-3. While this model of infection mimics some natural conditions in which infection takes place, other epidemiological conditions could favour entry of virus through the digestive tract. Here, we investigated whether ingestion of infectious materials mediates CyHV-3 entry through the digestive tract. Carp were fed with materials contaminated with the CyHV-3 LUC recombinant (oral contamination) or immersed in water containing the virus (contamination by immersion). Bioluminescence imaging analyses performed at different times post-infection led to the following observations: (i) the pharyngeal periodontal mucosa is the major portal of entry after oral contamination, while the skin is the major portal of entry after contamination by immersion. (ii) Both modes of inoculation led to the spreading of the infection to the various organs tested. However, the timing and the sequence in which some of the organs turned positive were different between the two modes of inoculation. Finally, we compared the disease induced by the two inoculation modes. They led to comparable clinical signs and mortality rate. The results of the present study suggest that, based on epidemiological conditions, CyHV-3 can enter carp either by skin or periodontal pharyngeal mucosal infection. [less ▲]

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See detailScaphandre La science rencontre l'art: L'art
Haubruge, Eric ULg; Bay, Daniel ULg; Semal, Jean et al

in Haubruge, Eric; Bay, Daniel; Semal, Jean (Eds.) Scaphandre La science rencontre l'art (2012)

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See detailGene expression analysis of common carp (Cyprinus carpio L.) lines during Cyprinid herpesvirus 3 infection yields insights into differential immune responses
Rakus; Irnazarow, I.; Adamek, M. et al

in Developmental & Comparative Immunology (2012), 37

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See detailBovine Herpesvirus Type 4 Glycoprotein L Is Nonessential for Infectivity but Triggers Virion Endocytosis during Entry
Lété, Céline ULg; Machiels, Bénédicte ULg; Stevenson, P. G. et al

in Journal of Virology (2012)

The core entry machinery of mammalian herpesviruses comprises glycoproteins B, H and L (gB, gH and gL). gH and gL form a heterodimer with a central role in viral membrane fusion. When archetypal alpha- or ... [more ▼]

The core entry machinery of mammalian herpesviruses comprises glycoproteins B, H and L (gB, gH and gL). gH and gL form a heterodimer with a central role in viral membrane fusion. When archetypal alpha- or beta-herpesviruses lack gL, gH misfolds and progeny virions are non-infectious. However, the gL of the rhadinovirus Murid herpesvirus 4 (MuHV-4) is non-essential for infection. In order to define more generally what role gL plays in rhadinovirus infections, we disrupted its coding sequence in Bovine herpesvirus-4 (BoHV-4). BoHV-4 lacking gL showed altered gH glycosylation and incorporated somewhat less gH into virions but remained infectious. However, gL- virions showed poor growth associated with an entry deficit. Moreover a major part of their entry defect appeared to reflect impaired endocytosis, which occurs upstream of membrane fusion itself. Thus, the rhadinovirus gL may be more important for driving virion endocytosis than for incorporating gH into virions, and is non-essential for membrane fusion. [less ▲]

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See detailProteomic characterization of bovine herpesvirus 4 extracellular virions.
Lété, Céline ULg; Palmeira, Leonor ULg; Leroy, Baptiste et al

in Journal of Virology (2012), 86(21), 11567-80

Gammaherpesviruses are important pathogens in human and animal populations. During early events of infection, these viruses manipulate preexisting host cell signaling pathways to allow successful ... [more ▼]

Gammaherpesviruses are important pathogens in human and animal populations. During early events of infection, these viruses manipulate preexisting host cell signaling pathways to allow successful infection. The different proteins that compose viral particles are therefore likely to have critical functions not only in viral structures and in entry into target cell but also in evasion of the host's antiviral response. In this study, we analyzed the protein composition of bovine herpesvirus 4 (BoHV-4), a close relative of the human Kaposi's sarcoma-associated herpesvirus. Using mass spectrometry-based approaches, we identified 37 viral proteins associated with extracellular virions, among which 24 were resistant to proteinase K treatment of intact virions. Analysis of proteins associated with purified capsid-tegument preparations allowed us to define protein localization. In parallel, in order to identify some previously undefined open reading frames, we mapped peptides detected in whole virion lysates onto the six frames of the BoHV-4 genome to generate a proteogenomic map of BoHV-4 virions. Furthermore, we detected important glycosylation of three envelope proteins: gB, gH, and gp180. Finally, we identified 38 host proteins associated with BoHV-4 virions; 15 of these proteins were resistant to proteinase K treatment of intact virions. Many of these have important functions in different cellular pathways involved in virus infection. This study extends our knowledge of gammaherpesvirus virions composition and provides new insights for understanding the life cycle of these viruses. [less ▲]

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