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See detailGenital re-excretion of Murid gammaherpesvirus 4 following intranasal infection
François, Sylvie ULg; Vidick, Sarah ULg; Sarlet, Michaël ULg et al

Poster (2011, November 16)

Gammaherpesviruses are the archetypes of persistent viruses that have been identified in a range of animals from mice to man. As the human gammaviruses have no well-established in vivo infection model ... [more ▼]

Gammaherpesviruses are the archetypes of persistent viruses that have been identified in a range of animals from mice to man. As the human gammaviruses have no well-established in vivo infection model, related animal gammaherpesviruses are an important source of information. We are studying Murid herpesvirus 4 (MuHV-4) in inbred laboratory mouse strains which are commonly accepted as a good model for studying gammaherpesviruses in vivo. To date, it has however never been possible to monitor viral reexcretion and virus transmission in this species. In order to identify potential re-excretion sites, intranasally infected mice were followed through global luciferase imaging for up to six months after infection. Surprisingly, we detected transient viral replication in mice genital tract at various times after latency establishment. Ex vivo imaging, quantitative PCR and immunohistochemistry revealed that virus genomes were present in high quantity in the vaginal tissue and that viral replication occurred mainly at the vaginal external border. Moreover, we highlighted the presence of free infectious viruses in the vaginal cavity at the moment of the observation of viral replication. As this ephemeral viral reexcretion could reveal a link with reproductive cycle, we compared reexcretion in normal and ovariectomized mice. Interestingly, no viral reactivation was observed in absence of hormonal cycle. In conclusion, we experimentally indentified for the first time a reexcretion site for MuHV-4 in mice that had been intranasaly infected. In the future, these results could help us to better understand the biology of gammaherpesviruses but should also allow us to develop strategies that could prevent the spread of these viruses in natural populations. [less ▲]

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See detailChemR23 dampens lung inflammation and enhances anti-viral immunity in a mouse model of acute viral pneumonia
Bondue, Benjamin; Vosters, Olivier; de Nadai, Patricia et al

in PLoS Pathogens (2011), 7(11), 1002358

Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells ... [more ▼]

Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells play an important role in anti-viral immunity, and these cells were recently shown to express ChemR23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. Our aim was to determine the role played by the chemerin/ChemR23 system in the physiopathology of viral pneumonia, using the pneumonia virus of mice (PVM) as a model. Wild-type and ChemR23 knock-out mice were infected by PVM and followed for functional and inflammatory parameters. ChemR23(-/-) mice displayed higher mortality/morbidity, alteration of lung function, delayed viral clearance and increased neutrophilic infiltration. We demonstrated in these mice a lower recruitment of plasmacytoid dendritic cells and a reduction in type I interferon production. The role of plasmacytoid dendritic cells was further addressed by performing depletion and adoptive transfer experiments as well as by the generation of chimeric mice, demonstrating two opposite effects of the chemerin/ChemR23 system. First, the ChemR23-dependent recruitment of plasmacytoid dendritic cells contributes to adaptive immune responses and viral clearance, but also enhances the inflammatory response. Second, increased morbidity/mortality in ChemR23(-/-) mice is not due to defective plasmacytoid dendritic cells recruitment, but rather to the loss of an anti-inflammatory pathway involving ChemR23 expressed by non-leukocytic cells. The chemerin/ChemR23 system plays important roles in the physiopathology of viral pneumonia, and might therefore be considered as a therapeutic target for anti-viral and anti-inflammatory therapies. [less ▲]

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See detailGenetic and splice variations of Bos taurus CD46 shift cell permissivity to BVDV, the bovine pestivirus.
Zezafoun, Hussein ULg; Decreux, Annabelle; Desmecht, Daniel ULg

in Veterinary Microbiology (2011), 152(3-4), 315-27

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 the existence of ten distinct allelic versions of the CCP1 module, varying significantly in frequency among taurine and indicine races. A complex mRNA splicing pattern was also evidenced for bovine CD46, generating three different serine-threonine-proline segments and five different cytoplasmic domains. The four most frequent allelic variants and the six splice variants were then expressed in BVDV-nonpermissive porcine cells and the quantity of progeny virions generated by each cell preparation was measured 48 h post-infection. As expected, ectopic expression of the 10 bovine CD46 isoforms rendered the PK15 cells permissive to BVDV, as attested by the 100,000-fold greater recovery of virions from these cells than from non-transfected cells. This permissivity increase was significantly lower (-33%, P<0.001) when the canonical CCP1 was replaced with the variant most frequent in zebus, suggesting positive or negative selection of this allele in the latter and in the former, respectively. The predicted secondary structure of this variant suggests that the measured loss of function is due to the disappearance of one of the two beta sheets constituting the BVDV attachment platform. On the other hand we showed that for a given CCP1, the titer recovered at 48 hpi also depended on the nature of the CD46 cytoplasmic domain (P<0.001). This result implies that virus binding generates a cytoplasmic-tail-dependent outside-in signal that determines permissivity to BVDV. [less ▲]

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See detailUpdate on Bovine neonatal pancytopenia non Pregsure cases
Theron, Léonard ULg; Rollin, Frédéric ULg; Hanzen, Christian ULg et al

Conference (2011, September 07)

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See detailPost-mortem examination and laboratory-based analysis for the diagnosis of bovine tuberculosis among dairy cattle in Ecuador
Proano-Perez, F.; Benitez-Ortiz, Washington; Desmecht, Daniel ULg et al

in Preventive Veterinary Medicine (2011), 101(1-2), 65-72

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See detailClinical evaluation of cardiac effects of experimental doxycycline overdosing in healthy calves
Brihoum, Mounir ULg; Rollin, Frédéric ULg; Desmecht, Daniel ULg et al

in Biomedcentral Veterinary Research (2011), 7

Background Cardiac morphologic and functional changes consistent with cardiomyopathy have been reported in field cases of calves with accidental doxycycline overdosing. The purpose of this study was to ... [more ▼]

Background Cardiac morphologic and functional changes consistent with cardiomyopathy have been reported in field cases of calves with accidental doxycycline overdosing. The purpose of this study was to evaluate clinically the cardiac effects of an experimentally-induced doxycycline overdosing in healthy calves. Twelve 2 months-old healthy Belgian Blue calves were studied. Six of them (group 1) received the normal dose (5 mg/kg, BID) and the six others (group 2) received five times the normal dose (25 mg/kg, BID) of oral doxycycline for five consecutive days (D1 to D5). Each calf was clinically examined daily. Measurement of serum AST, CK, Iso-CKs and LDH activities and an echocardiographic examination were performed before (D0) and one day after (D6) the last doxycycline administration. An ECG tracing was recorded at D0, D4, and D6. Results In both groups, no clinical, blood, echocardiographic or electrocardiographic changes suggestive of a cardiomyopathy were observed. Only a decreased appetite was observed in the calves of the group 2 between D3 and D6. Conclusions This trial failed to reproduce cardiac changes reported in accidental doxycycline-poisoning in calves, suggesting that high doses of doxycycline may not be the only etiologic factor of the cardiomyopathy reported in the field cases. [less ▲]

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See detailDetection of Anaplasma phagocytophilum in Dermacentor reticulatus ticks
Wirtgen, Marc ULg; Nahayo, A.; Linden, Annick ULg et al

in Veterinary Record : Journal of the British Veterinary Association (2011), 168(9), 248

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See detailImmune depression of the SJL/J mouse, a radioresistant and immunologically atypical inbred strain.
Glineur, Stéphanie ULg; Antoine-Moussiaux, Nicolas ULg; Michaux, Charles ULg et al

in Immunobiology (2011), 216(1-2), 213-217

As the inbred mouse strain SJL/J displays increased resistance to several pathogens and as its immune system shows multiple specificities, it is tempting to infer a causal link between these observations ... [more ▼]

As the inbred mouse strain SJL/J displays increased resistance to several pathogens and as its immune system shows multiple specificities, it is tempting to infer a causal link between these observations. The first question that comes to mind is whether adaptive immunity plays a role, and a way to answer this question is to see if the resistance phenotype persists when adaptive immunity is depressed. Although it has long been known that irradiation causes repression of leukopoiesis in mice, the technical data available in the literature are of no help in the case of strain SJL/J, because it displays exceptional radioresistance. Here we show that exposure of SJL/J to ∼9Gy, an intensity corresponding to the lethal dose 50 for the species Mus musculus, leads to serious but reversible alteration of leukopoiesis. This conclusion stems from an examination of the effects, 1-11 days post-exposure, of whole-body gamma-ray irradiation on leukocyte populations in the thymus and peripheral blood of young adult females. Immunodepression was most severe 4 days post-exposure. As in other strains, leukocyte populations displayed differential radiosensitivity, B (CD19(+)) cells being most sensitive, T (CD4(+)/CD8(+)) cells moderately sensitive, and natural killer (NK1.1(+)) cells most resistant. Surprisingly, however, the helper/inducer T lymphocytes proved more resistant than the cytotoxic/suppressor T lymphocytes, contrarily to what is observed in other strains. The procedure described will make it possible to refute or establish reliably the existence of causal links between SJL-specific phenotypic traits and immune aberrations and to elucidate further the respective roles of innate and acquired immunity in determining the resistance of this strain to an array of viral diseases. [less ▲]

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See detailN-acetylcysteine lacks universal inhibitory activity against influenza A viruses.
Garigliany, Mutien-Marie ULg; Desmecht, Daniel ULg

in Journal of negative results in biomedicine (2011), 10(1), 5

ABSTRACT: N-acetylcysteine (NAC) has been recently proposed as an adjuvant therapeutic drug for influenza pneumonia in humans. This proposal is based on its ability to restrict influenza virus replication ... [more ▼]

ABSTRACT: N-acetylcysteine (NAC) has been recently proposed as an adjuvant therapeutic drug for influenza pneumonia in humans. This proposal is based on its ability to restrict influenza virus replication in vitro and to attenuate the severity of the disease in mouse models. Although available studies were made with different viruses (human and avian), published information related to the anti-influenza spectrum of NAC is scarce. In this study, we show that NAC is unable to alter the course of a fatal influenza pneumonia caused by inoculation of a murinized swine H1N1 influenza virus. NAC was indeed able to inhibit the swine virus in vitro but far less than reported for other strains. Therefore, susceptibility of influenza viruses to NAC appears to be strain-dependent, suggesting that it cannot be considered as a universal treatment for influenza pneumonia. [less ▲]

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See detailMethodology of the biological risk classification of animal pathogens in Belgium
Van Vaerenbergh, B.; Koenen, Frank; Pauwels, K. et al

in Revue Scientifique et Technique / Office International des Epizooties = Revista Cientifica y Tecnica / Officina Internacional de Epizootias = Scientific and Technical Review / International Office of Epizootics (2010), 29(3), 513-522

The biological hazards posed by micro-organisms have lead to their categorisation into risk groups and the elaboration of classification lists. Current classification systems rely on criteria defined by ... [more ▼]

The biological hazards posed by micro-organisms have lead to their categorisation into risk groups and the elaboration of classification lists. Current classification systems rely on criteria defined by the World Health Organization, considering the severity of the disease the micro-organism might cause, its ability to spread and the availability of prophylaxis or efficient treatment. Animal pathogens are classified according to the definitions of the World Organization of Animal Health whereby also economic aspects are considered. In Europe, classification is often directly linked to containment measures. The Belgian classification however, considers only the inherent characteristics of the micro-organism, not its use, making it independent of containment measures. Also a common list for human and animal pathogens is elaborated, allowing a comprehensive approach. Evolution of scientific knowledge requires regular updating of classification lists. This paper describes the particularities of the Belgian classification and the methodology that was used for its peer-reviewed revision, hereby focusing on animal pathogens. [less ▲]

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See detailGenital re-excretion of Murid gammaherpesvirus 4 following intranasal infection
François, Sylvie ULg; Vidick, Sarah ULg; Sarlet, Michaël ULg et al

Poster (2010, November 18)

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

Gammaherpesviruses are the archetypes of persistent viruses that have been identified in a range of animals from mice to man. They are host-range specific and establish persistent, productive infections of immunocompetent hosts. Thus, infected individuals simultaneously both elicit antiviral protective immune response and secrete infectious virions. The best studied gammaherpesviruses are Human herpesvirus 4 and Human herpesvirus 8. As these viruses have no well-established in vivo infection model, related animal gammaherpesviruses are an important source of information. We are studying Murid herpesvirus 4 (MuHV-4), a virus that has originally been isolated from bank voles (Myodes glareolus). Although MuHV-4 has not been isolated from house mice (Mus musculus), infection of inbred laboratory mouse strains is commonly accepted as a good model for studying gammaherpesviruses in vivo. To date, it has however never been possible to monitor viral reexcretion and virus transmission in this species suggesting that this model could be imperfect. In order to identify potential re-excretion sites, intranasally infected mice were followed through global luciferase imaging for up to six months after infection. By this technique, we were able to detect appearance of viral replication in mice genital tract at various times post-infection. Typically, it firstly occurred between days 20 to 30 after infection, a period at which it is admitted that latency is established. Ex vivo imaging, quantitative PCR and immunohistochemistry helped us to determine that virus genomes were present in high quantity in the vaginal tissue and that viral replication occurred mainly at the vaginal external border. Finally, we highlighted the presence of free infectious viruses in the vaginal cavity at the moment of the observation of viral replication. In conclusion, we experimentally indentified for the first time a reexcretion site for MuHV-4 in mice that had been intranasaly infected. It therefore suggests potential genital transmission, either horizontal or vertical, of this virus in mice populations. In the future, these results could help us to better understand the biology of gammaherpesviruses but should also allow us to develop vaccinal strategies that could prevent the spread of these viruses in natural populations. [less ▲]

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See detailInfluenza A strain-dependent pathogenesis in fatal H1N1 and H5N1 infections of mice
Garigliany, Mutien-Marie ULg; Habyarimana, Jean ULg; Lambrecht, Bénédicte et al

in Emerging Infectious Diseases (2010), 16(4), 595-603

Two different influenza A viruses showing no pathogenicity towards the laboratory mouse were forced to evolve by serial passaging. Although both adapted viruses evoked diffuse alveolar damage and showed a ... [more ▼]

Two different influenza A viruses showing no pathogenicity towards the laboratory mouse were forced to evolve by serial passaging. Although both adapted viruses evoked diffuse alveolar damage and showed a similar 50% mouse lethal dose and the same peak lung concentration, they elicited dramatically different pathological signatures and ARDS courses. In the absence of any virus labeling, a histologist unaware of which infection he was looking at could readily distinguish infections caused by these two viruses. This suggests that fatal infections caused by different highly virulent influenza A viruses do not necessarily share the same pathogenesis. The different histological pictures shown here refute the hypothesis of a single, universal “cytokine storm” underlying all fatal influenzal diseases. Research is thus crucially needed to identify underlying sets of virulence markers and to examine whether it might be advantageous to tailor treatment to the influenza virus pathotype. [less ▲]

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See detailInterferon-induced Sus scrofa Mx1 blocks endocytic traffic of incoming influenza A virus particles
Palm, Mélanie; Garigliany, Mutien-Marie ULg; Cornet, François ULg et al

in Veterinary Research (2010), 41(3), 29

The interferon-induced Mx proteins of vertebrates are dynamin-like GTPases, some isoforms of which can additionally inhibit the life cycle of certain RNA viruses. Here we show that the porcine Mx1 protein ... [more ▼]

The interferon-induced Mx proteins of vertebrates are dynamin-like GTPases, some isoforms of which can additionally inhibit the life cycle of certain RNA viruses. Here we show that the porcine Mx1 protein (poMx1) inhibits replication of influenza A virus and we attempt to identify the step at which the viral life cycle is blocked. In infected cells expressing poMx1, the level of transcripts encoding the viral nucleoprotein is significantly lower than normal, even when secondary transcription is prevented by exposure to cycloheximide. This reveals that a pretranscriptional block participates to the anti-influenza activity. Binding and internalization of incoming virus particles are normal in the presence of poMx1 but centripetal traffic to the late endosomes is interrupted. Surprisingly but decisively, poMx1 significantly alters binding of early endosome autoantigen 1 to early endosomes and/or early endosome size and spatial distribution. This is compatible with impairment of traffic of the endocytic vesicles to the late endosomes. [less ▲]

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See detailComparative study of Murid gamma-herpesvirus 4 infection in mice and in a natural host, the bank voles.
François, Sylvie ULg; Vidick, Sarah ULg; Sarlet, Michaël ULg et al

in Journal of General Virology (The) (2010)

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

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

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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 detailDescriptive study of 32 cases of doxycycline-overdosed calves.
Brihoum, Mounir ULg; Amory, Hélène ULg; Desmecht, Daniel ULg et al

in Journal of Veterinary Internal Medicine (2010), 24(5), 1203-10

BACKGROUND: Reports of doxycycline-induced toxicity are limited despite common use of this antibiotic to treat infectious respiratory disorders in calves. OBJECTIVE: To describe previously unreported ... [more ▼]

BACKGROUND: Reports of doxycycline-induced toxicity are limited despite common use of this antibiotic to treat infectious respiratory disorders in calves. OBJECTIVE: To describe previously unreported kidney lesions and diagnostic test results in doxycycline-overdosed calves and to compare these results with other findings reported previously. ANIMALS: Thirty-two calves that presented with adverse effects after receiving high doses of doxycycline as a treatment for mild respiratory disorders. METHOD: Retrospective review of medical records. RESULTS: Clinical examination identified mainly lethargy, dyspnea, cough, tongue paresia or paralysis associated with dysphagia and sialorrhea, tachycardia, tachypnea, and signs of myopathy. Blood analysis indicated increases in creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and sorbitol dehydrogenase activities and increased serum creatinine and urea concentrations. ECG recordings and Doppler echocardiography examination identified ventricular premature beats and a decrease in left ventricular global and systolic function, respectively. Necropsy and histopathology disclosed necrosis of the myocardium, tongue, and some striated muscles, acute renal tubular necrosis, and fatty degeneration or congestion of the liver. CONCLUSIONS: Most of these findings corroborate previous observations made in doxycycline-overdosed calves, and further suggest myocardial and striated muscular toxicity as well as renal toxicity in doxycycline-overdosed calves. [less ▲]

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See detailComparative study of Murid gammaherpesvirus 4 infection in mice and in its natural host, the bank voles.
François, Sylvie ULg; Vidick, Sarah ULg; Koteja, Pawel et al

Poster (2009, December 11)

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

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

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See detailPorcine CD18 mediates Actinobacillus pleuropneumoniae ApxIII species-specific toxicity
Vanden bergh, Philippe; Zecchinon, Laurent; Fett, Thomas ULg et al

in Veterinary Research (2009), 40(4), 33

Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, produces Apx toxins that are recognized as major virulence factors. Recently, we showed that ApxIIIA-cytotoxic activity ... [more ▼]

Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, produces Apx toxins that are recognized as major virulence factors. Recently, we showed that ApxIIIA-cytotoxic activity specifically targets Sus scrofa leukocytes. Since both LtxA from Aggregatibacter actinomycetem comitans (aggressive periodontitis in humans) and LktA from Mannheimia haemolytica (pneumonia in ruminants) share this characteristic, respectively towards human and ruminant leukocytes, and because both use the CD18 subunit to interact with their respective LFA-1, we hypothesized that ApxIIIA was likely to bind porcine CD18 to exercise its deleterious effects on pig leukocytes. A beta(2)-integrin-deficient ApxIIIA-resistant human erythroleukemic cell line was transfected either with homologous or heterologous CD11a/ CD18 heterodimers using a set of plasmids coding for human (ApxIIIA-resistant), bovine (-resistant) and porcine (-susceptible) CD11a and CD18 subunits. Cell preparations that switched from ApxIIIA-resistance to -susceptibility were then sought to identify the LFA-1 subunit involved. The results showed that the ApxIIIA-resistant recipient cell line was rendered susceptible only if the CD18 partner within the LFA-1 heterodimer was that of the pig. It is concluded that porcine CD18 is necessary to mediate A. pleuropneumoniae ApxIIIA toxin-induced leukolysis. [less ▲]

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See detailSurra-induced lymphopenia is directly triggered by a membrane-associated parasite protein
Antoine-Moussiaux, Nicolas ULg; Cornet, Anne ULg; Cornet, François et al

Conference (2009, May 24)

Detailed reference viewed: 14 (7 ULg)