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See detailNew use of VEGF in therapeutics: application in tendon lesions
Kaux, Jean-François ULg; Le Goff, Caroline ULg; Drion, Pierre ULg et al

in Clinical Chemistry (2010, July), 56(S6), 111

Introduction: As demonstrated in previous studies, mechanical overload, injury and inflammation, hypoxic condition or any combination of the above could lead to increased expression of VEGF in the tendon ... [more ▼]

Introduction: As demonstrated in previous studies, mechanical overload, injury and inflammation, hypoxic condition or any combination of the above could lead to increased expression of VEGF in the tendon. Thus, VEGF could participate in the healing of pathological tendons. Indeed, some authors are convinced that this neovascularization is the sign of a chronic tendinopathy while others plead in favour of it being a sign of healing processes. The VEGF111, which is a biologically active and proteolysis-resistant VEGF-A isoform, was recently identified. It is induced by ultraviolet B and genotoxic drugs. Experimentation shows that, in nude mice, tumors formed by HEK293 cells expressing VEGF111 develop a more widespread peritumoral neovascularisation than those expressing other VEGF isoforms. Good angiogenic activity and resistance to proteolysis makes VEGF111 a potential beneficial therapeutic option for ischemic diseases. The aim of our study was to determine whether if VEGF111 could have a therapeutic interest in the framework of tendinous pathology. Methods (*): A 5mm defect was surgically induced in Achilles tendon of 60 rats. Rats were divided into 2 groups of 30: A: a control group (no injection) and B: with a VEGF111 injection. The rats of group B received an injection of 100 ng of VEGF111 in situ 1 hour after surgery on the site of the tendon lesion. Afterwards, rats of both groups were placed in their cages without immobilization. After 5, 15 and 30 days, 10 rats of each group were euthanized. The traumatized Achilles tendon of each rat was dissected and removed. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a tensile machine with “Cryo-jaw”. Statistical analyses were made with an ANOVA. Results: A significant increase over time of the force necessary to induce tendon rupture was observed for tendons which had been submitted to an injection of VEGF111 (p=0.016). The force required to break the tendon is always greater for the VEGF111 group (p<0.05). Discussion: We demonstrated that the force necessary to induce the rupture of a rat’s Achilles tendon during biomechanical tensile testing was greater for tendons which had been submitted to an injection of VEGF111. Thus, this experimentation showed that VEGF111 injections could accelerate the tendon healing process and increase the force needed to break tendons in their healing process. Conclusion: VEGF111 could be a new therapy for tendon lesions. However, other experimentation using a rat model with different concentrations of VEGF111 should be made to ascertain the best concentration for this healing process. Acknowledgement: This experimentation was partially financed by “Standard de Liège” and “Lejeune-Lechien” grants. (*) All experimental procedures and protocols used in this investigation were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Liège. [less ▲]

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See detailComparison between platelet-rich plasma (PRP) and vascular endothelial growth factor-111 (VEGF-111) as a therapeutic tool in tendon healing process
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent ULg et al

Poster (2010, March 20)

Introduction In spite of the availability of various treatments for tendinopathy, this pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Among them, the ... [more ▼]

Introduction In spite of the availability of various treatments for tendinopathy, this pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Among them, the injection of platelet-rich plasma (PRP) seems to be a promising one. Indeed, several animal models have demonstrated that injection of blood platelets can initiate and stimulate tendon and ligament repair by releasing growth factors (GF) locally. Among all the GF released by activated platelets, the vascular endothelial growth factor-A (VEGF-A) is known to induce positive effects on vascular function and angiogenesis, and could be implicated in the healing process of tendons. Recently, a novel VEGF-A isoform was identified, the VEGF-111, a biologically active and proteolysis-resistant VEGF-A isoform, also known to present beneficial effects on ischemic diseases. This prompted us to evaluate whether VEFF-111 would have a therapeutic interest within the framework of the tendon pathology. Aim of the study: We hypothesized that the healing of ruptured Achilles tendons, which is the last stage of the Blazina’s classification, could be improved by injection of VEGF-111 that was compared to the potential effect of PRP injections using a rat model. Methods: A 5mm defect was surgically induced in rat Achilles tendon after resection of plantaris tendon. Rats were divided into 3 groups: A: control (no injection), B: PRP treatment and C: VEGF-111 treatment. Rats received a local injection of PRP (50µL) or VEGF-111 (100ng) in situ after the surgery and were placed in their cage without immobilization. After 5, 15 and 30 days, the rats were euthanized in each group. The traumatized Achilles tendon of each rat was removed and dissected during the healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Results: Our results show that developed force necessary to induce tendon rupture during biomechanical tensile test was more important for tendons which had received an injection of PRP or VEGF-111. Moreover, the tensile force necessary to break tendons is higher with PRP than with VEGF-111. These results were already noticed from day 5 onwards. Conclusion: This experimentation has shown that both PRP and VEGF-111 injections stimulated tendon healing process as suggested by the increased force needed to break tendons during its healing process. Furthermore, this acceleration of the cicatrisation process was more significant with PRP than with VEGF-111. This could be explained by the release from platelets of a “cocktail” of growth factors acting in synergy on the healing process. Acknowledgement This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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See detailPlatelet-rich plasma (PRP) increases healing process of rats' Achilles tendons
Kaux, Jean-François ULg; Drion, Pierre ULg; Pascon, Frédéric ULg et al

Conference (2010, March 20)

Introduction Some tendinopathies (epicondylitis, jumper’s knee or Achilles tendinopathy) are frequently considered as rebel to “classic” treatments such as rest, orthotics, NSAIs, electrotherapy ... [more ▼]

Introduction Some tendinopathies (epicondylitis, jumper’s knee or Achilles tendinopathy) are frequently considered as rebel to “classic” treatments such as rest, orthotics, NSAIs, electrotherapy, physiotherapy, corticosteroid infiltrations, extracorporeal shock waves… Recently, several studies, essentially in vitro, demonstrated the positive effects of platelets on the healing process of different tissues: bones, muscles and tendons. Objectives The aim of our experiment was to ascertain whether the use of platelet-rich plasma (PRP) was of interest for accelerating the healing process of Achilles tendon after surgical induced lesion. Methods A 5mm defect was surgically induced in rat Achilles tendon after resection of plantaris tendon. Rats were divided into 2 groups: A: control (no injection) and B: PRP injection. Rats of group B received a PRP injection in situ after the surgery. Afterwards, rats of both groups were placed in their cage without immobilization. After 5, 15 and 30 days, rats were euthanized. The traumatized Achilles tendon of each rat was removed and dissected during this healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Results We demonstrated that the force necessary to induce tendon rupture during biomechanical tensile test study was more important for tendons which had been submitted to an injection of PRP. These results were noticed from day 5 onwards. Discussion – Conclusion This experimentation has shown that PRP injections could accelerate tendons healing process and increase the force needed to break tendons in their healing process. This “accelerating” process can be observed as early as day 5. Acknowledgement This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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See detailViral induction of Zac1b through TLR3- and IRF3-dependent pathways
Warzée, Barbara ULg; Mesnil, Claire ULg; Hober, D. et al

in Molecular Immunology (2010), 48(1-3), 119-127

Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important ... [more ▼]

Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important potential functions attributed to Zac1, little is known of its physiological regulation and biological function. We discovered that variant Zac1b was expressed in murine embryonic fibroblasts (MEFs) treated with polyriboinosinic polyribocytidylic acid [poly(I:C)], a synthetic double-stranded RNA. This regulation occurred mainly through Toll-Like Receptor 3 (TLR3)- and Interferon Regulatory Factor 3 (IRF3)-dependent pathways. As TLR3 and IRF3 are central activators of antiviral immunity, we hypothesized that Zac1 may be implicated in antiviral responses. In line with this notion, we observed that Zac1b was expressed in MEFs infected with Encephalomyocarditis virus (EMCV). We also observed that Zac1-deficient MEFs were less sensitive to EMCV-induced cell death than wild-type MEFs. However, Zac1 gene inactivation had no effect on the survival of mice infected with EMCV. In conclusion, this study describes for the first time a transcriptional regulation of Zac1b, induced by synthetic dsRNA and RNA viruses, the functional significance of which remains to be further investigated. [less ▲]

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See detailThe use of an adapted model allows contributing to the “Reduction” of mice used in experimental protocols: the case of the apoE–deficient (apo E-/-) mice in a model of atherosclerosis control
Cherdon, Céline ULg; Rolin, Stéphanie; de Leval, Laurence ULg et al

Poster (2009, December 01)

Atherosclerosis is a chronic vascular disease whose development is influenced by several mediators 1. Among them, the prostanoids large family lipids generated from the metabolism of arachidonic acid by ... [more ▼]

Atherosclerosis is a chronic vascular disease whose development is influenced by several mediators 1. Among them, the prostanoids large family lipids generated from the metabolism of arachidonic acid by the action of COX includes various types of PGs and thromboxane. Thromboxane A2 and PGI2 are present in abnormally elevated concentration in atherosclerosis 2-3. To exert its effects TXA2 and its precursor PGH2 act at a specific receptor termed TP receptor 4. As a result, TXA2 synthase inhibitors and TP antagonists have been developed to reduce and to prevent TXA2 production and actions, respectively. The present study was undertaken in order to investigate whether BM-573, an original sulfonylurea derivate synthesized in our lab 5, and aspirin would be effective in preventing the progression of atherosclerosis in an apo E deficient mouse model. [less ▲]

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See detailLe PRP (Platelet-Rich Plasma) peut-il favoriser la régénération tendineuse ?
Kaux, Jean-François ULg; Drion, Pierre ULg; Pascon, Frédéric ULg et al

in Annales de Réadaptation et de Médecine Physique (2009, October), 52(Sup. 1), 109-110

Introduction : Certaines tendinopathies (l’épicondylite, la tendinopathie rotulienne supérieure ou encore la tendinopathie d’Achille) demeurent rebelles malgré un traitement « classique » bien conduit ... [more ▼]

Introduction : Certaines tendinopathies (l’épicondylite, la tendinopathie rotulienne supérieure ou encore la tendinopathie d’Achille) demeurent rebelles malgré un traitement « classique » bien conduit : repos, orthèse, AINS, électrothérapie, kinésithérapie, infiltrations de corticoïdes, ondes de choc... Certains travaux, essentiellement in vitro, soulignent les potentialités réparatrices des plaquettes qui présentent la capacité d’accélérer la cicatrisation de différents tissus : os, muscles et tendons. Objectifs : Le but de notre étude préliminaire est d’objectiver l’effet « accélérateur » sur la réparation tendineuse suite à l’emploi d’injection de plasma enrichi en plaquettes (platelet-rich plasma ou PRP) car cette technique pourrait représenter une thérapeutique d’avenir en médecine physique et en traumatologie du sport. Méthodes : Nous avons sectionné et réalisé un défect de 5mm dans le tendon d’Achille de rats (N = 12). Quatre rats ont bénéficié d’une injection in loco de PRP et remis en liberté comme les autres dans leur cage. Trois rats (2 sans PRP et 1 avec PRP) sont euthanasiés à J5, J10, J20 et J30 et le tendon d’Achille en cours de régénération est disséqué et prélevé. Une étude biomécanique de traction jusqu’à rupture est réalisé à l’aide de « Cryo-jaw ». Résultats : L’analyse des résultats montre que la force développée pour obtenir la rupture tendineuse doit être plus importante pour les tendons ayant bénéficié d’une injection de PRP et ce dès J5. Discussion – Conclusion : Cette série préliminaire permet de montrer que les injections de PRP permettent une accélération de la cicatrisation tendineuse et une augmentation des valeurs de résistances à la traction. Une étude avec un plus grand nombre de sujets est en cours. [less ▲]

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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 ▲]

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See detailLe bm-573, un antagoniste original du récepteur au thromboxane a2, réduit le développement des lésions athéromateuses chez des souris déficientes en apolipoprotéine e (apo e-/-) contrairement a l’aspirine.
Cherdon, Céline ULg; Rolin, Stéphanie; Ooms, Annie ULg et al

(2009, May 28)

Afin d’examiner l'efficacité de l’aspirine et du BM-573 dans l'athérogenèse, des souris apo E-/- femelles ont été traitées durant 10 et 20 semaines avec le BM-573 (10mg/kg/j), l’aspirine (30mg/kg/j) ou un ... [more ▼]

Afin d’examiner l'efficacité de l’aspirine et du BM-573 dans l'athérogenèse, des souris apo E-/- femelles ont été traitées durant 10 et 20 semaines avec le BM-573 (10mg/kg/j), l’aspirine (30mg/kg/j) ou un placébo. Au cours de cette expérience, aucune modification du poids corporel ou de la cholestérolémie n’a été observée. Par contre, le traitement des animaux par le BM-573, a eu pour effet de diminuer les lésions athéromateuses de manière significative tandis que l’aspirine a été sans effet sur ce paramètre. Ces données ont été confirmées par des analyses histopathologiques et biochimiques. Ces résultats confirment que l'antagonisme sélectif des récepteurs TP associé à une inhibition de la thromboxane synthétase réduit significativement les lésions athéromateuses chez les souris apo E-/-. Le BM-573 est, par conséquent, un agent thérapeutique potentiel pour la prévention de l'athérosclérose. [less ▲]

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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 ▲]

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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)

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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)

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See detailReconstitution du système immunitaire après allogreffe de cellules souches hématopoïétiques
Castermans, Emilie ULg; Hannon, Muriel ULg; Drion, Pierre ULg et al

in Revue Médicale de Liège (2009), 64(S1), 2-8

Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient ... [more ▼]

Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient tumors cells by donor immune cells contained in the graft (graft-versus-tumor effects), underlying the interest of stydying donor immune recovery after alloHCT. Further, donor immune cells play an important role in the prevention and treatment of infections after allHCT, and are the cause of graft-versus-host disease (GVHD). This article reviews the mechanisms of immune recovery after allogeneic hematopoietic cell transplantation (alloHCT), as well as techniques currently used to monitor immune function following allHCT. [less ▲]

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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)

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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 ▲]

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See detailStudy of thromboxane modulators in a murine model of atherosclerosis
Cherdon, Céline ULg; Rolin, Stéphanie; de Leval, Laurence ULg et al

(2008, July 04)

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See detailEvolution of anti-eCG antibodies in response to eCG doses and number of injections. Relation with rabbit does productivity
Theau-Clément, M.; Lebas, F.; Beckers, J. F. et al

in Animal (2008), 2(5), 746-751

The aim of this experiment was to study the kinetics of anti-eCG (equine chorionic gonadotrophin) antibodies in relation to eCG dose (8 or 25 IU) and number of injections (n = 11) in comparison with a ... [more ▼]

The aim of this experiment was to study the kinetics of anti-eCG (equine chorionic gonadotrophin) antibodies in relation to eCG dose (8 or 25 IU) and number of injections (n = 11) in comparison with a control group (no injection), and to relate antibody production to sexual receptivity and productivity of rabbit does. In all, 124 lactating primiparous rabbit does were inseminated every 35 days for a year. Just before eCG injection (48 h before insemination), blood samples were collected from all the does to assay anti-eCG antibodies. The anti-eCG antibody binding rate, regardless of the injected dose, shows that none of the does developed detectable anti-eCG antibodies before the 7th injection. The level of detectable anti-eCG antibodies began to show an increase at the 7th injection and was significant only for the 25 IU dose at the 11th injection. At the end of the experiment, 15% and 39% of does treated with 8 and 25 IU, respectively, developed immunity to eCG (binding rate >6%: higher binding rate of the control group). Consequently, the immune response depends on the eCG dose and on the number of injections. Moreover, productivity of does estimated from the number of weaned rabbits produced per insemination is not influenced by the level of eCG antibodies (7.0 and 6.9 for binding rate <6% and binding rate 6%, respectively). Only 19 inseminations (n = 6 and n = 13 for 8 and 25 IU, respectively) were made on hyperimmune does. Consequently, the immune response to eCG seems to be marginal for rabbit does. Moreover, under the described experimental conditions, reproductive performances of hyperimmune does were not affected [less ▲]

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See detailLung interstitial macrophages prevent lipopolysaccharide-triggered T helper type 2 responses to harmless inhaled antigens
Bedoret, D.; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Proceedings of the Annual BIS-meeting (2008)

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See detailCloning of the koi herpesvirus genome as an infectious bacterial artificial chromosome demonstrates that disruption of the thymidine kinase locus induces partial attenuation in Cyprinus carpio koi.
Costes, Bérénice ULg; Fournier, Guillaume ULg; Michel, Benjamin ULg et al

in Journal of Virology (2008), 82(10), 4955-4964

Koi herpesvirus (KHV) is the causative agent of a lethal disease in koi and common carp. In the present study, we describe the cloning of the KHV genome as a stable and infectious bacterial artificial ... [more ▼]

Koi herpesvirus (KHV) is the causative agent of a lethal disease in koi and common carp. In the present study, we describe the cloning of the KHV genome as a stable and infectious bacterial artificial chromosome (BAC) clone that can be used to produce KHV recombinant strains. This goal was achieved by the insertion of a loxP-flanked BAC cassette into the thymidine kinase (TK) locus. This insertion led to a BAC plasmid that was stably maintained in bacteria and was able to regenerate virions when permissive cells were transfected with the plasmid. Reconstituted virions free of the BAC cassette but carrying a disrupted TK locus (the FL BAC-excised strain) were produced by the transfection of Cre recombinase-expressing cells with the BAC. Similarly, virions with a wild-type revertant TK sequence (the FL BAC revertant strain) were produced by the cotransfection of cells with the BAC and a DNA fragment encoding the wild-type TK sequence. Reconstituted recombinant viruses were compared to the wild-type parental virus in vitro and in vivo. The FL BAC revertant strain and the FL BAC-excised strain replicated comparably to the parental FL strain. The FL BAC revertant strain induced KHV infection in koi carp that was indistinguishable from that induced by the parental strain, while the FL BAC-excised strain exhibited a partially attenuated phenotype. Finally, the usefulness of the KHV BAC for recombination studies was demonstrated by the production of an ORF16-deleted strain by using prokaryotic recombination technology. The availability of the KHV BAC is an important advance that will allow the study of viral genes involved in KHV pathogenesis, as well as the production of attenuated recombinant candidate vaccines. [less ▲]

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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 ULg; Farnir, Frédéric ULg et al

in PLoS ONE (2008), 3(2), 1627

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-29-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 postinoculation. (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 ▲]

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See detailInfluence of the Ixodes ricinus tick blood-feeding on the antigen-specific antibody response in vivo.
Menten-Dedoyart, Catherine ULg; Couvreur, B.; Thellin, Olivier ULg et al

in Vaccine (2008), 26(52), 6956-64

The blood meal of hard ticks such as Ixodes ricinus lasts several days. This is made possible by tick salivary factors that inhibit inflammation, haemostasis and the host immune response. We assessed the ... [more ▼]

The blood meal of hard ticks such as Ixodes ricinus lasts several days. This is made possible by tick salivary factors that inhibit inflammation, haemostasis and the host immune response. We assessed the latter on a model of immune response in vivo. A significant reduction of specific IgM and IgG levels was observed in BALB/c mice infested 5 days before injection with bovine serum albumin (BSA) and QuilA but not in mice infested 5 days after the immunization. This effect was not observed in mock-infested mice and could not be attributed to the use of anesthetics. The antibody response was not merely delayed and the Th(1)/Th(2) balance appeared not altered. T-dependent zones and germinal centers in lymph nodes draining the tick bite site showed no apparent morphological alterations or shift in T cell subpopulations. However, the spleens of tick-infested mice had also an enlarged red pulp, indicating an increased extramedullary haematopoietic activity. [less ▲]

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