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See detailClinical and haematological alterations in foot and mouth disease virus naturally-infected domestic water buffaloes in Vietnam
Dam Van Phai, ULiege; BUI TRAN ANH, Dao, ; Desmecht, Daniel ULiege

Poster (2017, October 13)

Foot and mouth disease (FMD) has been one of the most important epizootic diseases in several cloven-hoofed animals including buffaloes, causing severe economic losses in Vietnam. This study aimed at ... [more ▼]

Foot and mouth disease (FMD) has been one of the most important epizootic diseases in several cloven-hoofed animals including buffaloes, causing severe economic losses in Vietnam. This study aimed at observing clinical indicators, physiological parameters, haematological and blood chemistry values of 30 buffaloes naturally infected with FMD virus (FMDV). The study was undertaken from January 2015 to February 2016 in Hanoi, Vietnam. Results show that buffaloes infected with FMDV displayed significantly higher fever, increased respiratory rate and increased heart frequency compared to healthy animals. Moreover, FMDV-infected animals always showed high fever and vesicular stomatitis, often showed edging nail congestive inflammation and, sometimes only, blisters on the nipple. Haematological indicators showed that FMDV-infected buffaloes were dehydrated (increased total protein). Besides, infected animals also underwent anaemia as mean corpuscular haemoglobin and mean corpuscular haemoglobin concentrations were plummeted. Total white blood cell count plummeted too, especially the number and proportion of neutrophils. Meanwhile, the number and proportion of lymphocytes sharply increased compared to healthy animals. Infected buffaloes also displayed signs of liver and heart damages as judged by an increase in concentration of AST and ALT, while there was not renal damage since creatinine concentration remained stable [less ▲]

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See detailATYPICAL DICTYOCAULUS VIVIPAROUS-ASSOCIATED BOVINE ACUTE PNEUMONITIS: REMINISCENT OF LARVAL HYPOBIOSIS DURING THE WINTER?
Bayrou, Calixte ULiege; Dernier, Adrienne ULiege; Cassart, Dominique ULiege et al

Conference (2017, October)

Dictyocaulus viviparus is the aetiological agent of verminous bronchitis in cattle. Herein we describe an atypical case of parasitic pneumonitis in an adult cow. Methods At the end of March 2017, a 3-yr ... [more ▼]

Dictyocaulus viviparus is the aetiological agent of verminous bronchitis in cattle. Herein we describe an atypical case of parasitic pneumonitis in an adult cow. Methods At the end of March 2017, a 3-yr old Belgian Blue cow suddenly displayed a marked respiratory distress syndrome a few hours after C-section calving. In spite of the treatment set up by the local veterinarian, the cow died 48 hours later. The body was referred to the Veterinary Faculty of Liège (Belgium) for necropsy. Post- mortem gross examination revealed a severe, acute interstitial pneumonitis with concurrent emphysema and a significant amount of parasites (Dictyocaulus viviparus) in the bronchi. The microscopic examination confirmed the severe acute interstitial pneumonitis with foci of hemorrhages, necrosis, hyaline membranes and hyperplasia of type II pneumocytes. Larvae were also present in the alveoli and bronchioles. Results Altogether, theses clinical observations and lesions were compatible with a hypersensitivity reaction against worm antigens. Additionally, Baermann’s test was performed on feces collected from the cadaver and from 5 others cows kept under the same conditions. Four out of 6 cows were excreting small amounts of Dictyocaulus stage-1 larvae. Conclusions Parasitic pneumonia is a very common disease in first year grazing young cattle. In this case, cow’s age and disease manifestation time were very uncommon. Three-year-old cows are supposed to be fully protected against this nematode species. Moreover, in Belgium, at the end of March, livestock is still kept indoors (zero grazing winter period). Therefore, this case could highlight the hypobiotic capacity of Dictyocaulus viviparus larvae and associated « periparturient rise » phenomenon, both well known in sheep, but not described in cattle so far. We herein discuss the farming conditions that promoted such a severe parasitic respiratory disease. [less ▲]

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See detailCryopreservation of chicken primordial germ cells by vitrification and slow-freezing: a comparative study
Tonus, Céline ULiege; Connan, Delphine ULiege; Waroux, Olivier ULiege et al

in Theriogenology (2017), 88

In the present study, we compare a classical slow freezing method and an aseptic vitrification technique to cryopreserve a stable Primordial Gem Cells (PGCs) line issued from the Ardennaise chicken breed ... [more ▼]

In the present study, we compare a classical slow freezing method and an aseptic vitrification technique to cryopreserve a stable Primordial Gem Cells (PGCs) line issued from the Ardennaise chicken breed. Viability immediately after warming was close to 80% and did not differ between the two cryopreservation methods. Proliferation tended to be slower for both cryopreservation methods compared to controls, but the difference was significant only for vitrification. No difference was found between the two methods after flow cytometry analysis of SSEA-1 expression and RT-PCR on several factors related to PGCs phenotype. After one week in culture, all cryopreserved cells reached controls main morphological and expanding (viability/proliferation) features. However, slow freezing generated more unwanted cells clusters than vitrification. After injection of the PGCs into recipient embryos, vitrified PGCs showed a clear, yet not significant, tendency to colonize the gonad at a higher rate than slow frozen PGCs. Slow freezing in cryovials remains simple, inexpensive and less technically demanding than vitrification. Nevertheless, the intrinsic advantages of our aseptic vitrification method and the present study suggest that this should be considered as safer than classical slow freezing for cryopreserving chicken PGCs. [less ▲]

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See detailUsutu virus, Belgium, 2016
Garigliany, Mutien-Marie ULiege; Linden, Annick ULiege; Gilliaux, Gautier ULiege et al

in Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases (2017), 48(1), 116-119

During late summer 2016, in a northwest European region extending over Belgium, the Netherlands and the eastern border of the German state of North Rhine Westphalia, an outbreak of wild bird deaths ... [more ▼]

During late summer 2016, in a northwest European region extending over Belgium, the Netherlands and the eastern border of the German state of North Rhine Westphalia, an outbreak of wild bird deaths occurred similar to those reported on the continent since 1996. Dead birds were necropsied and examined by complementary methods. Pathologic and immunohistological investigations strongly suggested an infection by Usutu virus. Subsequently, genomic segments of the said virus were detected, the virus was isolated and its complete genome was sequenced. The strain, designated Usutu-LIEGE, is a close phylogenetic relative of those isolated in Germany which form a distinct group within the USUV phylogeny, the so-called Europe_3 lineage. Should this outbreak recapitulate the characteristics of those in southwest Germany in 2011 and in/around Vienna (Austria) in 2001, it is expected that specific avian populations in the affected area will face a significant reduction in size for a few years. [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 detailMoku Virus in Invasive Asian Hornets, Belgium, 2016.
Garigliany, Mutien-Marie ULiege; Taminiau, Bernard ULiege; El Agrebi, Noémie ULiege et al

in Emerging Infectious Diseases (2017), 23(12), 2109-2112

We report the detection of Moku virus in invasive Asian hornets (Vespa velutina nigrithorax) in Belgium. This constitutes an unexpected report of this iflavirus outside Hawaii, USA, where it was recently ... [more ▼]

We report the detection of Moku virus in invasive Asian hornets (Vespa velutina nigrithorax) in Belgium. This constitutes an unexpected report of this iflavirus outside Hawaii, USA, where it was recently described in social wasps. Although virulence of Moku virus is unknown, its potential spread raises concern for European honeybee populations. [less ▲]

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See detailWidespread activity of multiple lineages of Usutu virus, western Europe, 2016.
Cadar, Daniel; Luhken, Renke; van der Jeugd, Henk et al

in Euro Surveillance : Bulletin Européen sur les Maladies Transmissibles = European Communicable Disease Bulletin (2017), 22(4),

In the summer of 2016, Belgium, France, Germany and the Netherlands reported widespread Usutu virus (USUV) activity based on live and dead bird surveillance. The causative USUV strains represented four ... [more ▼]

In the summer of 2016, Belgium, France, Germany and the Netherlands reported widespread Usutu virus (USUV) activity based on live and dead bird surveillance. The causative USUV strains represented four lineages, of which two putative novel lineages were most likely recently introduced into Germany and spread to other western European countries. The spatial extent of the outbreak area corresponded with R0 values > 1. The occurrence of the outbreak, the largest USUV epizootic registered so far in Europe, allowed us to gain insight in how a recently introduced arbovirus with potential public health implications can spread and become a resident pathogen in a naive environment. Understanding the ecological and epidemiological factors that drive the emergence or re-emergence of USUV is critical to develop and implement timely surveillance strategies for adequate preventive and control measures. Public health authorities, blood transfusion services and clinicians in countries where USUV was detected should be aware of the risk of possible USUV infection in humans, including in patients with unexplained encephalitis or other neurological impairments, especially during late summer when mosquito densities peak. [less ▲]

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See detailCell cycle S phase markers are expressed in cerebral neuron nuclei of cats infected by the Feline Panleukopenia Virus
Poncelet, Luc; Garigliany, Mutien-Marie ULiege; Ando et al

in Cell Cycle (Georgetown, Tex.) (2016), 15(24), 3482-3489

The cell cycle-associated neuronal death hypothesis, which has been proposed as a common mechanism for most neurodegenerative diseases, is notably supported by evidencing cell cycle effectors in neurons ... [more ▼]

The cell cycle-associated neuronal death hypothesis, which has been proposed as a common mechanism for most neurodegenerative diseases, is notably supported by evidencing cell cycle effectors in neurons. However, in naturally occurring nervous system diseases, these markers are not expressed in neuron nuclei but in cytoplasmic compartments. In other respects, the Feline Panleukopenia Virus (FPV) is able to complete its cycle in mature brain neurons in the feline species. As a parvovirus, the FPV is strictly dependent on its host cell reaching the cell cycle S phase to start its multiplication. In this retrospective study on the whole brain of 12 cats with naturally-occurring, FPV-associated cerebellar atrophy, VP2 capsid protein expression was detected by immunostaining not only in some brain neuronal nuclei but also in neuronal cytoplasm in 2 cats, suggesting that viral mRNA translation was still occurring. In these cats, double immunostainings demonstrated the expression of cell cycle S phase markers cyclin A, cdk2 and PCNA in neuronal nuclei. Parvoviruses are able to maintain their host cells in S phase by triggering the DNA damage response. S139 phospho H2A1, a key player in the cell cycle arrest, was detected in some neuronal nuclei, supporting that infected neurons were also blocked into the S phase. PCR studies did not support a co-infection with an adeno or herpes virus. ERK1/2 nuclear accumulation was observed in some neurons suggesting that the ERK signaling pathway might be involved as a mechanism driving these neurons far into the cell cycle. [less ▲]

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See detailSoluble forms of CD46 are detected in Bos taurus plasma and neutralize BVDV, the bovine pestivirus
Alzamel, Nidal ULiege; Bayrou, Calixte ULiege; Decreux, Annabelle et al

in Comparative Immunology, Microbiology and Infectious Diseases (2016), 49

The pestivirus bovine viral diarrhea virus (BVDV) is known to bind to the CD46 molecule, which subsequently promotes entry of the virus. Mapping of the BVD-virion-binding site has shown that two peptides ... [more ▼]

The pestivirus bovine viral diarrhea virus (BVDV) is known to bind to the CD46 molecule, which subsequently promotes entry of the virus. Mapping of the BVD-virion-binding site has shown that two peptides, 66EQIV69 and 82GQVLAL87, located on antiparallel beta sheets in the most distal complement control protein module (CCP1), provide the attachment platform. In the present study, we reveal new CD46-encoding transcripts that are predicted to encode CCP1-containing soluble forms. Further, we show that the serum of most adult cattle contains soluble CD46 (sCD46) and that a recombinant soluble isoform neutralizes BVDV infectivity in an in vitro assay. We have then established an ELISA for determination of plasma sCD46 in a large cohort of animals. Overall, serum sCD46 amounts to 8 ± 18 ng/mL (mean ± SD, n = 440), with a IC [95-105] ranging from 6,4 to 9,8 ng/mL and extreme values between 0 and 178 ng/mL. We found that sCD46 is not detectable in fetal and neonatal sera and that its plasma concentration increases progressively up to adulthood. We also detected high- and low-sCD46 performers and show that this phenotype does not depend of environment. As modern rearing techniques make it possible to disseminate genetically-determined phenotypes very quickly in a population, a large-scale study examining whether high-sCD46 animals provide epidemiological protection against BVDV infection and transmission should be undertaken. [less ▲]

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See detailRe-emergence of the Schmallenberg virus associated triad hydranencephaly-micromyelia-arthrogryposis in a newborn calf in Belgium, 2016
Bayrou, Calixte ULiege; Garigliany, Mutien-Marie ULiege; Cassart, Dominique ULiege et al

in Veterinary Record Case Reports (2016), 4(1), 000342

Schmallenberg virus (SBV) emerged in Germany in 2011, then spread rapidly across Europe, causing an epizootic outbreak of abortion, stillbirth and birth at term of lambs, kids and calves with neurological ... [more ▼]

Schmallenberg virus (SBV) emerged in Germany in 2011, then spread rapidly across Europe, causing an epizootic outbreak of abortion, stillbirth and birth at term of lambs, kids and calves with neurological signs and/or musculo-skeletal malformations. SBV-associated disease in newborns disappeared in Belgium in 2013. Here, we describe a SBV genomic RNA-positive malformed calf born in May 2016. It reveals the return of SBV circulation during the fall 2015 in the said area. [less ▲]

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See detailLong term-cultured and cryopreserved primordial germ cells from various chicken breeds retain high proliferative potential and gonadal colonisation competency
Tonus, Céline ULiege; Cloquette, Karine; Ectors, Fabien ULiege et al

in Reproduction, Fertility and Development (2016), 28(5), 628-639

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See detailMeningitis and orchitis in a hare (Lepus Europaeus) infected with Francisella tularensis
Grégoire, Fabien; Cassart, Dominique ULiege; Desmecht, Daniel ULiege et al

in Veterinary Records Case Reports (2016), 4(e000306),

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See detailFeline panleukopenia virus in cerebral neurons of young and adult cats.
Garigliany, Mutien-Marie ULiege; Gilliaux, Gautier ULiege; Jolly, Sandra et al

in BMC veterinary research (2016), 12(1), 28

BACKGROUND: Perinatal infections with feline panleukopenia virus (FPV) have long been known to be associated with cerebellar hypoplasia in kittens due to productive infection of dividing neuroblasts. FPV ... [more ▼]

BACKGROUND: Perinatal infections with feline panleukopenia virus (FPV) have long been known to be associated with cerebellar hypoplasia in kittens due to productive infection of dividing neuroblasts. FPV, like other parvoviruses, requires dividing cells to replicate which explains the usual tropism of the virus for the digestive tract, lymphoid tissues and bone marrow in older animals. RESULTS: In this study, the necropsy and histopathological analyses of a series of 28 cats which died from parvovirus infection in 2013 were performed. Infections were confirmed by real time PCR and immunohistochemistry in several organs. Strikingly, while none of these cats showed cerebellar atrophy or cerebellar positive immunostaining, some of them, including one adult, showed a bright positive immunostaining for viral antigens in cerebral neurons (diencephalon). Furthermore, infected neurons were negative by immunostaining for p27(Kip1), a cell cycle regulatory protein, while neighboring, uninfected, neurons were positive, suggesting a possible re-entry of infected neurons into the mitotic cycle. Next-Generation Sequencing and PCR analyses showed that the virus infecting cat brains was FPV and presented a unique substitution in NS1 protein sequence. Given the role played by this protein in the control of cell cycle and apoptosis in other parvoviral species, it is tempting to hypothesize that a cause-to-effect between this NS1 mutation and the capacity of this FPV strain to infect neurons in adult cats might exist. CONCLUSIONS: This study provides the first evidence of infection of cerebral neurons by feline panleukopenia virus in cats, including an adult. A possible re-entry into the cell cycle by infected neurons has been observed. A mutation in the NS1 protein sequence of the FPV strain involved could be related to its unusual cellular tropism. Further research is needed to clarify this point. [less ▲]

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See detailRisk factors and effect of selective removal on retroviral infections prevalence in Belgian stray cats.
Garigliany, Mutien-Marie ULiege; Jolly, Sandra ULiege; Dive, M. et al

in The Veterinary record (2016), 178(2), 45

The aim of this study was to evaluate the effect of several risk/protective factors and predictors on the prevalence of feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) infections in ... [more ▼]

The aim of this study was to evaluate the effect of several risk/protective factors and predictors on the prevalence of feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) infections in 302 stray cats captured during a trap-neuter-release programme in a mixed urban-rural area from Belgium, from 2010 to 2012. The impact of selective removal of FIV-positive cats on the apparent prevalence in the remaining population over this three-year period was also assessed. The seroprevalences over three years were 18.8 per cent for FIV and 0.7 per cent for FeLV. For FIV, the seroprevalence decreased significantly from the first year of the programme (2010; 30.5 per cent) to the last (2012; 13.1 per cent). Sex (male) and age (adult and old cats) were risk factors, while the year of sampling (years 2011 and 2012) was a protective factor. Age, sex and location were the most relevant predictors of FIV status. The data presented in this study revealed a very high FIV seroprevalence in Belgian stray cats, while FeLV was almost absent. The selective removal of positive cats had a drastic effect on the FIV seroprevalence in the remaining cat population. [less ▲]

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See detailLong term culture, cryopreservation and genetic modification of chicken primordial germ cells
Tonus, Céline ULiege; Garcia Gil, Francisco José ULiege; Cloquette, Karine et al

Poster (2015, October 16)

Avian primordial germ cells (PGCs) are precursor of gametes and appear during early stages of embryonic development. Under appropriate culture conditions, these cells can keep their germ cells properties ... [more ▼]

Avian primordial germ cells (PGCs) are precursor of gametes and appear during early stages of embryonic development. Under appropriate culture conditions, these cells can keep their germ cells properties in vitro and are foreseen as promising tools for developing efficient avian genetic engineering and preservation of germplasm. We propose original methods that allow long term expansion, efficient cryopreservation and genetic modification of primary cultures of undifferentiated PGCs. PGCs are collected from embryonic blood during their migratory period and grown in cell-culture insert in the presence of feeder cells (BRL). This physically separated co-culture system along with selective culture medium promoted emergence, selection and proliferation of PGCs lines. Forty percent of blood samples gave rise to lines originating from three commercial layer and two Belgian endangered breeds. PGCs lines were characterized for the expression of the stem cells and PGCs marker SSEA-1 by FACS. RT-PCR confirmed expression of germ-line specific markers (CVH, CDH, DAZL), pluripotency markers (cPouV, cSox2, cNanog), telomerase and CXCR4 receptor. All lines were male although isolated from pooled male and female blood samples. Two cryopreservation methods were developed based upon slow-freezing and aseptic vitrification. Both have shown a similar effectiveness in allowing storage without phenotype drift. Stably expressing lines were obtained by Lipofectamine® mediated transfection of a GFP plasmid. PGCs were subsequently injected in recipient embryos. Persistence of exogenous PGCs in the developing gonad of recipient embryos confirmed that PGCs retain their gonadal colonisation ability, both after long-term culture and after cryopreservation. [less ▲]

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See detailHyporeactivity of Alveolar Macrophages and Higher Respiratory Cell Permissivity Characterize DBA/2J Mice Infected by Influenza A Virus Hyporeactivity of Alveolar Macrophages and Higher Respiratory Cell Permissivity Characterize DBA/2J Mice Infected by Influenza A Virus.
Casanova Bustos, Tomas Ronaldo ULiege; Van de Paar, Els; Desmecht, Daniel ULiege et al

in JOURNAL OF INTERFERON & CYTOKINE RESEARCH (2015), 35(10), 808-820

Influenza A virus remains a major public health problem. Mouse models have been widely used to study influenza infection in mammals. DBA/2J and C57BL/6J represent extremes in terms of susceptibility to ... [more ▼]

Influenza A virus remains a major public health problem. Mouse models have been widely used to study influenza infection in mammals. DBA/2J and C57BL/6J represent extremes in terms of susceptibility to influenza A infection among inbred laboratory mouse strains. Several studies focused specifically on the factors responsible for the susceptibility of DBA/2J or the resistance of C57BL/6J and resulted in impressive lists of candidate genes or factors over- or underexpressed in one of the strains. We adopted a different phenotypical approach to identify the critical steps of the infection process accounting for the differences between DBA/2J and C57BL/6J strains. We concluded that both a dysfunction of alveolar macrophages and an increased permissivity of respiratory cells rendered DBA/2J more susceptible to influenza infection. [less ▲]

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See detailRational Development of an Attenuated Recombinant Cyprinid Herpesvirus 3 Vaccine Using Prokaryotic Mutagenesis and In Vivo Bioluminescent Imaging
Boutier, Maxime ULiege; Ronsmans, Maygane ULiege; Ouyang, Ping et al

in PLoS Pathogens (2015), 11(2), 1004690

Cyprinid herpesvirus 3 (CyHV 3) is causing severe economic losses worldwide in common and koi carp industries, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We ... [more ▼]

Cyprinid herpesvirus 3 (CyHV 3) is causing severe economic losses worldwide in common and koi carp industries, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We produced single deleted recombinants using prokaryotic mutagenesis. When producing a recombinant lacking open reading frame 134 (ORF134), we unexpectedly obtained a clone with additional deletion of ORF56 and ORF57. This triple deleted recombinant replicated efficiently in vitro and expressed an in vivo safety/efficacy profile compatible with use as an attenuated vaccine. To determine the role of the double ORF56-57 deletion in the phenotype and to improve further the quality of the vaccine candidate, a series of deleted recombinants was produced and tested in vivo. These experiments led to the selection of a double deleted recombinant lacking ORF56 and ORF57 as a vaccine candidate. The safety and efficacy of this strain were studied using an in vivo bioluminescent imaging system (IVIS), qPCR, and histopathological examination, which demonstrated that it enters fish via skin infection similar to the wild type strain. However, compared to the parental wild type strain, the vaccine candidate replicated at lower levels and spread less efficiently to secondary sites of infection. Transmission experiments allowing water contamination with or without additional physical contact between fish demonstrated that the vaccine candidate has a reduced ability to spread from vaccinated fish to naïve sentinel cohabitants. Finally, IVIS analyses demonstrated that the vaccine candidate induces a protective mucosal immune response at the portal of entry. Thus, the present study is the first to report the rational development of a recombinant attenuated vaccine against CyHV 3 for mass vaccination of carp. We also demonstrated the relevance of the CyHV 3 carp model for studying alloherpesvirus transmission and mucosal immunity in teleost skin. [less ▲]

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See detailA role for APPL1 in tlr3/4-dependent TBK1 and IKKε activation in macrophages
Chau, Tieu-Lan ULiege; Göktuna, Serkan ULiege; Rammal, Ayman et al

in Journal of Immunology (2015)

Endosomes have important roles in intracellular signal transduction as a sorting platform. Signaling cascades from TLR engagement to IRF3-dependent gene transcription rely on endosomes, yet the proteins ... [more ▼]

Endosomes have important roles in intracellular signal transduction as a sorting platform. Signaling cascades from TLR engagement to IRF3-dependent gene transcription rely on endosomes, yet the proteins that specifically recruit IRF3-activating molécules to them are poorly defined. We show that adaptor protein containing a pleckstrin-homology domain, a phosphotyrosine-binding domain, and a leucine zipper motif (APPL)1, an early endosomal protein, is required for both TRIF- and retinoic acid–inducible gene 1–dependent signaling cascades to induce IRF3 activation. APPL1, but not early endosome Ag 1, deficiency impairs IRF3 target gene expression upon engagement of both TLR3 and TLR4 pathways, as well as in H1N1-infected macrophages. The IRF3-phosphorylating kinases TBK1 and IKK« are recruited to APPL1 endosomes in LPS-stimulated macrophages. Interestingly, APPL1 undergoes proteasome-mediated degradation through ERK1/2 to turn off signaling. APPL1 degradation is blocked when signaling through the endosome is inhibited by chloroquine or dynasore. Therefore, APPL1 endosomes are critical for IRF3-dependent gene expression in response to some viral and bacterial infections in macrophages. Those signaling pathways involve the signal-induced degradation of APPL1 to prevent aberrant IRF3-dependent gene expression linked to immune diseases. [less ▲]

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See detailThe alpha2,3-Sialyltransferase Encoded by Myxoma Virus Is a Virulence Factor that Contributes to Immunosuppression.
Boutard, Berengere; Vankerckhove, Sophie; Markine-Goriaynoff, Nicolas et al

in PloS one (2015), 10(2), 0118806

Myxoma virus (MYXV) induces a lethal disease called Myxomatosis in European rabbits. MYXV is one of the rare viruses that encodes an alpha2,3-sialyltransferase through its M138L gene. In this study, we ... [more ▼]

Myxoma virus (MYXV) induces a lethal disease called Myxomatosis in European rabbits. MYXV is one of the rare viruses that encodes an alpha2,3-sialyltransferase through its M138L gene. In this study, we showed that although the absence of the enzyme was not associated with any in vitro deficit, the M138L deficient strains are highly attenuated in vivo. Indeed, while all rabbits infected with the parental and the revertant strains died within 9 days post-infection from severe myxomatosis, all but one rabbit inoculated with the M138L deficient strains survived the infection. In primary lesions, this resistance to the infection was associated with an increased ability of innate immune cells, mostly neutrophils, to migrate to the site of virus replication at 4 days post-infection. This was followed by the development of a better specific immune response against MYXV. Indeed, at day 9 post-infection, we observed an important proliferation of lymphocytes and an intense congestion of blood vessels in lymph nodes after M138L knockouts infection. Accordingly, in these rabbits, we observed an intense mononuclear cell infiltration throughout the dermis in primary lesions and higher titers of neutralizing antibodies. Finally, this adaptive immune response provided protection to these surviving rabbits against a challenge with the MYXV WT strain. Altogether, these results show that expression of the M138L gene contributes directly or indirectly to immune evasion by MYXV. In the future, these results could help us to better understand the pathogenesis of myxomatosis but also the importance of glycans in regulation of immune responses. [less ▲]

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