%0 Journal Article %J Int J Food Microbiol %D 2023 %T Hepatitis E virus in pork meat products and exposure assessment in Belgium. %A Tatjana Locus %A Lambrecht, Ellen %A Michael Peeters %A Vanessa Suin %A Bavo Verhaegen %A Koenraad Van Hoorde %A Lamoral, Sophie %A Thomas Vanwolleghem %A Steven Van Gucht %X

Zoonotic hepatitis E virus (HEV) genotype 3 infections are the predominant cause of acute viral hepatitis in Europe, mostly associated with the consumption of HEV contaminated pork meat. In this study we looked at the HEV RNA positivity rate of pork meat products readily available from Belgian supermarkets and evaluated the overall HEV consumer exposure in a Belgian context. Two basic assessments were performed in a 'worst-case' scenario setting: one solely focusing on the contamination level of the product itself (ingredients and processing parameters) and another estimating the overall consumer exposure, taking into account consumption habits in Belgium. Non-thermal-processed ready-to-eat (i.e. ready for consumption without additional cooking step by consumer) pork meat products (e.g. raw dried sausages), had a high estimated HEV contamination level, while thermal-processed ready-to-eat pork meat products (e.g. pork liver pâté) had the highest overall consumer exposure estimates. Following these assessments, pork liver pâtés, raw dried hams and raw dried sausages (n = 54) were purchased from Belgian supermarkets (n = 3) and analyzed for HEV RNA by RT-PCR. In total, 31 % (n = 17) products tested positive. HEV RNA was found in 65 % of the pork liver pâtés, 15 % of raw dried hams and 0 % of raw dried sausages. Phylogenetic analysis of four isolates (all gt3c) from pork liver pâté samples showed similarities with human clinical cases from Germany and Belgium.

%B Int J Food Microbiol %V 397 %8 2023 Apr 05 %G eng %R 10.1016/j.ijfoodmicro.2023.110198 %0 Report %D 2020 %T Epidemiologische surveillance van hepatitis B - 2018 %A Sofieke Klamer %A Chloé Wyndham-Thomas %A Vanessa Suin %K Hepatitis B %K Surveillance %X

 In 2018 hebben de peillaboratoria 2116 nieuwe gevallen van actieve infectie met het hepatitis B virus (HBV) gemeld, een iets hoger aantal dan tijdens de twee jaren voordien (2017, n=1650 2016, n=1662). Acute HBV-infecties komen het vaakst voor in de leeftijdsgroep 25-44 jaar: 53% van de nieuwe diagnoses geregistreerd door het netwerk van peillaboratoria waren in deze leeftijdsgroep. Onder de geregistreerde nieuwe HBV-infecties, is er een daling waargenomen van het aandeel gevallen jonger dan 25 jaar (de leeftijdsgroep die profiteerde van gratis vaccinatie, die in 1999 is gestart voor zuigelingen en jonge adolescenten). Dit zou een weerspiegeling kunnen zijn van het bestaande vaccinatiebeleid.

Het is aanbevolen om een register op te stellen van de patiënten die besmet zijn met HBV om de impact van het vaccinatieprogramma en het effect van de nieuwe behandelingen te volgen. Om virale hepatitis op termijn te elimineren als majeur volksgezondheidsprobleem, heeft de Wereldgezondheidsorganisatie (WGO) de volgende doelstellingen bepaald: daling met 90% van het aantal nieuwe diagnoses en met 65% van het aantal sterfgevallen als gevolg van virale hepatitis tegen 2030 (vergeleken met 2015).

%I Sciensano %C Brussel %P 6 %8 02/2020 %G eng %0 Journal Article %J International Journal of Infectious Diseases %D 2020 %T A new multiplex RT-qPCR method for the simultaneous detection and discrimination of Zika and chikungunya viruses %A Sylvia Broeders %A Linda Garlant %A Marie-Alice Fraiture %A Els Vandermassen %A Vanessa Suin %A Jessica Vanhomwegen %A Myrielle Dupont-Rouzeyrol %A Dominique Rousset %A Steven Van Gucht %A Nancy Roosens %K Chikungunya virus %K discrimination %K identification %K multiplex %K RT-qPCR %K Zika virus %X

Objective

The re-emergence and spread of tropical viruses to new areas has raised a wave of concern worldwide. In order to treat patients at an early stage and prevent the diffusion of an outbreak, early diagnosis, and therefore fast and adequate detection, is needed. To this end, a multiplex reverse transcription real-time polymerase chain reaction TaqMan method was designed to detect Zika (ZIKV) and chikungunya (CHIKV) viruses simultaneously.

Methods

Two methods targeting different genome segments were selected from the literature for each virus. These were adapted for high genome coverage and combined in a four-plex assay that was thoroughly validated in-house. The SCREENED tool was used to evaluate the sequence coverage of the method.

Results

The full validation approach showed that the new four-plex method allows the specific and sensitive identification and discrimination of ZIKV and CHIKV in routine samples. The combination of two targets per virus allowing almost 100% coverage of about 500 genomes is shown for the first time.

Conclusions

PCR is a reliable user-friendly technique that can be applied in remote areas. Such multiplex methods enable early and efficient diagnosis, leading to rapid treatment and effective confinement in outbreak cases. They may also serve as an aid for surveillance, and the full validation permits easy method-transfer allowing worldwide harmonization.

%B International Journal of Infectious Diseases %V 92 %8 Jan-03-2020 %G eng %R 10.1016/j.ijid.2019.12.028 %0 Journal Article %J BMC Veterinary Research %D 2020 %T Presence of antibodies against tick-borne encephalitis virus in sheep in Tunisia, North Africa. %A Khamassi Khbou, Médiha %A Romdhane, Rihab %A Asma Amina Foughali %A Sassi, Limam %A Vanessa Suin %A Mourad Rekik %A M’hammed Benzarti %B BMC Veterinary Research %V 16 %8 Jan-12-2020 %G eng %N 1 %R 10.1186/s12917-020-02651-6 %0 Report %D 2020 %T Surveillance épidémiologique de l’hépatite B - 2018 %A Sofieke Klamer %A Chloé Wyndham-Thomas %A Vanessa Suin %K epidemiology %K Hepatitis B %K Surveillance %X

En 2018, les laboratoires vigies ont rapporté 2116 nouveaux cas d’infection active par le virus de l’hépatite B (VHB), un nombre un peu plus élevé qu’au cours des deux années précédentes (2017, n=1650 2016, n=1662). Le VHB survient le plus souvent dans le groupe d’âge des 25-44 ans: 53 % des nouveaux diagnostics enregistrés se situaient dans cette tranche d’âge. Une diminution de la proportion des nouvelles infections par le VHB chez les moins de 25 ans (groupe d'âge ayant bénéficié de la gratuité de la vaccination, initiée en 1999 pour les nourrissons et les jeunes adolescents) est observée. Ceci pourrait être un reflet de la politique vaccinale en place.

Il est recommandé d’établir un registre des patients infectés par le VHB afin de suivre l’impact du programme de vaccination ainsi que l’effet des nouveaux traitements. Afin d’éliminer les hépatites virales comme problème de santé publique majeur, l’Organisation mondiale de la Santé (OMS) a défini comme objectifs la réduction de 90 % du nombre de nouveaux cas et la réduction de 65 % le nombre de décès dus à l’hépatite virale d’ici 2030 (par rapport à 2015).

%I Sciensano %C Bruxelles %P 6 %8 02/2020 %G eng %0 Journal Article %J Euro Surveill %D 2019 %T Epidemiology and genotype 3 subtype dynamics of hepatitis E virus in Belgium, 2010 to 2017. %A Vanessa Suin %A Sofieke Klamer %A Veronik Hutse %A Wautier, Magali %A Marjorie Meurisse %A Mona Abady %A Lamoral, Sophie %A Vera Verburgh %A Isabelle Thomas %A Bernard Brochier %A Lorenzo Subissi %A Steven Van Gucht %K hepatitis E; HEV; surveillance; epidemiology; genotype; Belgium %X

BackgroundHepatitis E virus (HEV) is an emerging public health concern in high-income countries and can cause acute and chronic hepatitis. Reported numbers of indigenously acquired HEV infection have increased in the past decade in many European countries. Since 2010, the National Reference Centre (NRC) for Hepatitis Viruses has been testing samples of suspected hepatitis E cases in Belgium.AimIn this surveillance report, we present the epidemiological trends of symptomatic HEV infections in Belgium, from the distribution by age, sex and geography to the molecular characterisation of the viral strains.MethodSerum samples of suspected cases sent to the NRC between 2010 and 2017 were analysed for the presence of HEV-specific IgM and RNA. Virus was sequenced for genotyping and phylogenetic analysis in all samples containing sufficient viral RNA.ResultsThe NRC reported an increase in the number of samples from suspected cases (from 309 to 2,663 per year) and in the number of laboratory-confirmed hepatitis E cases (from 25 to 117 per year). Among 217 sequenced samples, 92.6% were genotype 3 (HEV-3), followed by 6.5% of genotype 1 and 0.9% of genotype 4. HEV-3 subtype viruses were mainly 3f, 3c and 3e. HEV-3f was the most common subtype until 2015, while HEV-3c became the most common subtype in 2016 and 2017.ConclusionThe increasing trend of HEV diagnoses in Belgium may be largely explained by increased awareness and testing.

%B Euro Surveill %V 24 %8 2019 Mar %G eng %N 10 %R 10.2807/1560-7917.ES.2019.24.10.1800141 %0 Journal Article %J Acta gastro-enterologica Belgica %D 2019 %T Hepatitis C virus (HCV) prevalence estimation in the adult general population in Belgium : a meta-analysis %A Gaetan Muyldermans %A Rob Bielen %A R Botterman %A Stefan Bourgeois %A I Colle %A B Deressa %A G Devolder %A Horsmans, Yves %A Veronik Hutse %A Nicolas Lanthier %A Luc Lasser %A S Platteau %A Geert Robaeys %A Vanessa Suin %A Verhelst, Xavier %A H Vlierberghe %A L Van Baelen %B Acta gastro-enterologica Belgica %V 82 %8 2019/10/01 %G eng %0 Journal Article %J BMC Public Health %D 2019 %T Low hepatitis C prevalence in Belgium: implications for treatment reimbursement and scale up. %A Amber Litzroth %A Vanessa Suin %A Chloé Wyndham-Thomas %A Sophie Quoilin %A Gaetan Muyldermans %A Thomas Vanwolleghem %A Kabamba-Mukadi, Benoît %A Vera Verburgh %A Marjorie Meurisse %A Steven Van Gucht %A Veronik Hutse %X

BACKGROUND: Prevalence data of chronic hepatitis C virus (HCV) infection are needed to estimate the budgetary impact of reimbursement of direct-acting antivirals (DAAs). In Belgium, the restricted reimbursement criteria are mainly guided by regional seroprevalence estimates of 0.87% from 1993 to 1994. In this first Belgian nationwide HCV prevalence study, we set out to update the seroprevalence and prevalence of chronic HCV infection estimates in the Belgian general population in order to guide decisions on DAA reimbursement.

METHODS: Residual sera were collected through clinical laboratories. We collected data on age, sex and district. HCV antibody status was determined with ELISA and confirmed with a line-immunoassay (LIA). In specimens with undetermined or positive LIA result, HCV viral load was measured. Specimens were classified seronegative, seropositive with resolved infection, indicative of chronic infection and with undetermined HCV status according to the test outcomes. Results were standardized for age, sex and population per district, and adjusted for clustered sampling.

RESULTS: In total 3209 specimens, collected by 28 laboratories, were tested. HCV seropositivity in the Belgian general population was estimated to be 0.22% (95% CI: 0.09-0.54%), and prevalence of chronic HCV infection 0.12% (95% CI: 0.03-0.41). In individuals of 20 years and older, these estimates were 0.26% (95% CI: 0.10-0.64%) and 0.13% (95% CI: 0.04-0.43), respectively. Of the total estimated number of HCV seropositive individuals in Belgium, 66% were between 50 and 69 years old.

CONCLUSIONS: Prevalence of HCV seropositivity and chronic infection in the Belgian general population were low and comparable to many surrounding countries. These adjusted prevalences can help estimate the cost of reimbursement of DAAs and invite Belgian policy makers to accelerate the scaling up of reimbursement, giving all chronically infected HCV patients a more timely access to treatment.

%B BMC Public Health %V 19 %8 2019 Jan 08 %G eng %N 1 %R 10.1186/s12889-018-6347-z %0 Journal Article %J Int J Infect Dis %D 2019 %T A new multiplex RT-qPCR method for the simultaneous detection and discrimination of Zika and chikungunya viruses. %A Sylvia Broeders %A Linda Garlant %A Marie-Alice Fraiture %A Els Vandermassen %A Vanessa Suin %A Jessica Vanhomwegen %A Myrielle Dupont-Rouzeyrol %A Dominique Rousset %A Steven Van Gucht %A Nancy Roosens %K chikungunya %K VIRUS %K Zika %X

OBJECTIVE: The re-emergence and spreading of tropical viruses to new areas raised worldwide a wave of concern. To treat patients in an early stage and prevent diffusion of the outbreak, an early diagnosis, and thus fast and adequate detection, is needed. To this aim, a multiplex reverse transcription real-time polymerase chain reaction TaqMan® method was designed to detect universally Zika and chikungunya viruses.

DESIGN: Two methods, targeting different genome segments, were selected from literature for each virus, adapted for high genome coverage and joined into a four-plex assay which was thoroughly in-house validated. The SCREENED tool was used to evaluate the sequence coverage of the method.

RESULTS: The full validation approach showed that the new four-plex method allows specific and sensitive identification and discrimination of Zika and chikungunya in routine samples. The combination of two targets per virus allowing almost 100% coverage of about 500 genomes was shown for the first time.

CONCLUSION: PCR being a reliable user-friendly technique, applicable in remote areas, such multiplex methods enable early and efficient diagnosis leading to rapid treatment and effective confinement in outbreak cases as well as being an aid for surveillance and the full validation permits easy method-transfer allowing worldwide harmonization.

%B Int J Infect Dis %8 2019 Dec 26 %G eng %R 10.1016/j.ijid.2019.12.028 %0 Journal Article %J Parasites & Vectors %D 2019 %T Prevalence of pathogens in ticks collected from humans through citizen science in Belgium %A Tinne Lernout %A Nick De Regge %A Katrien Tersago %A Manoj Fonville %A Vanessa Suin %A Sprong, Hein %B Parasites & Vectors %V 12 %8 Jan-12-2019 %G eng %N 1 %R 10.1186/s13071-019-3806-z %0 Journal Article %J Epidemiol Infect %D 2019 %T Subtype-specific differences in the risk of hospitalisation among patients infected with hepatitis E virus genotype 3 in Belgium, 2010-2018. %A Lorenzo Subissi %A Michael Peeters %A Lamoral, Sophie %A Sofieke Klamer %A Vanessa Suin %A Steven Van Gucht %K hepatitits E %X

Some European countries recently reported an increase in hepatitis E virus genotype 3 (HEV-3) of the subtype 3c. No link between HEV-3 subtypes and severity is established to date. Here, we report that patients infected with HEV-3c were at lower risk of hospitalisation, compared to those infected with HEV-3f, the other main subtype circulating in Belgium.

%B Epidemiol Infect %V 147 %8 2019 Jan %G eng %R 10.1017/S0950268819001122 %0 Journal Article %J J Clin Virol %D 2018 %T Clinical burden of hepatitis E virus infection in a tertiary care center in Flanders, Belgium. %A Cattoir, Lien %A Van Hoecke, Frederik %A Van Maerken, Tom %A Nys, Eveline %A Ryckaert, Inge %A De Boulle, Matthias %A Geerts, Anja %A Verhelst, Xavier %A Colle, Isabelle %A Veronik Hutse %A Vanessa Suin %A Wautier, Magali %A Steven Van Gucht %A Van Vlierberghe, Hans %A Padalko, Elizaveta %X

BACKGROUND: Hepatitis E virus (HEV) infection is increasingly recognized as a cause of hepatitis in developed countries. A high HEV IgG seroprevalence in humans and pigs is reported as well as sporadic clinical cases of autochtonous HEV but there are currently no data available on the clinical burden of HEV in Belgium.

OBJECTIVES: The objective of the current study was to evaluate the actual clinical burden of HEV infections in our tertiary care center in Flanders, Belgium.

STUDY DESIGN: In the setting of Ghent University Hospital, patients were assessed for the presence of HEV IgG and IgM as well as HEV RNA if no other cause was found for one of the following clinical presentations: a) elevation of liver enzymes in post-liver transplant; b) suspicion of acute or toxic hepatitis; c) unexplainable elevation of liver enzymes; d) cirrhosis with acute-on-chronic exacerbation.

RESULTS: In a period of 39 months (January 2011-April 2014) 71 patients were enrolled. HEV IgG was found positive in 13 (18,3%) patients; HEV IgM in 6 patients (8,5%) and HEV RNA in 4 (5,6%) patients. All HEV IgM/RNA positive patients were male, aged 41-63, and classified in the clinical groups a), b) or d). HEV IgG seroprevalence was slightly higher but not significantly different from the seroprevalence in the general population in this region in Belgium previously reported to be 14% (p-value 0.41) by our group.

CONCLUSIONS: HEV should be considered as a cause of liver pathology especially in middle-aged men with elevation of liver enzymes.

%B J Clin Virol %V 103 %8 2018 Mar 19 %G eng %R 10.1016/j.jcv.2018.03.004 %0 Journal Article %J PLoS One %D 2018 %T Distribution of HCV genotypes in Belgium from 2008 to 2015. %A Lobna Bouacida %A Vanessa Suin %A Veronik Hutse %A Michaël Boudewijns %A Reinoud Cartuyvels %A Laurent Debaisieux %A Emmanuel De Laere %A Hallin, Marie %A Nicolas Hougardy %A Lagrou, Katrien %A Els Oris %A Padalko, Elizaveta %A Marijke Reynders %A Gatien Roussel %A Jean-Marc Senterre %A Michel Stalpaert %A Dominique Ursi %A Carl Vael %A Vaira, Dolorès %A Van Acker, Jos %A Walter Verstrepen %A Steven Van Gucht %A Kabamba, Benoît %A Sophie Quoilin %A Gaetan Muyldermans %K hepatitis C virus %X

BACKGROUND: The knowledge of circulating HCV genotypes and subtypes in a country is crucial to guide antiviral therapy and to understand local epidemiology. Studies investigating circulating HCV genotypes and their trends have been conducted in Belgium. However they are outdated, lack nationwide representativeness or were not conducted in the general population.

METHODS: In order to determine the distribution of different circulating HCV genotypes in Belgium, we conducted a multicentre study with all the 19 Belgian laboratories performing reimbursed HCV genotyping assays. Available genotype and subtype data were collected for the period from 2008 till 2015. Furthermore, a limited number of other variables were collected: some demographic characteristics from the patients and the laboratory technique used for the determination of the HCV genotype.

RESULTS: For the study period, 11,033 unique records collected by the participating laboratories were used for further investigation. HCV genotype 1 was the most prevalent (53.6%) genotype in Belgium, with G1a and G1b representing 19.7% and 31.6%, respectively. Genotype 3 was the next most prevalent (22.0%). Further, genotype 4, 2, and 5 were responsible for respectively 16.1%, 6.2%, and 1.9% of HCV infections. Genotype 6 and 7 comprise the remaining <1%. Throughout the years, a stable distribution was observed for most genotypes. Only for genotype 5, a decrease as a function of the year of analysis was observed, with respectively 3.6% for 2008, 2.3% for 2009 and 1.6% for the remaining years. The overall M:F ratio was 1.59 and was mainly driven by the high M:F ratio of 3.03 for patients infected with genotype 3. Patients infected with genotype 3 are also younger (mean age 41.7 years) than patients infected with other genotypes (mean age above 50 years for all genotypes). The patients for whom a genotyping assay was performed in 2008 were younger than those from 2015. Geographical distribution demonstrates that an important number of genotyped HCV patients live outside the Belgian metropolitan cities.

CONCLUSION: This national monitoring study allowed a clear and objective view of the circulating HCV genotypes in Belgium and will help health authorities in the establishment of cost effectiveness determinations before implementation of new treatment strategies. This baseline characterization of the circulating genotypes is indispensable for a continuous surveillance, especially for the investigation of the possible impact of migration from endemic regions and prior to the increasing use of highly potent direct-acting antiviral (DAA) agents.

%B PLoS One %V 13 %8 2018 %G eng %N 12 %R 10.1371/journal.pone.0207584 %0 Journal Article %J Euro Surveill %D 2018 %T Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017. %A Patricia Ndumbi %A Gudrun S Freidl %A Christopher J Williams %A Otilia Mårdh %A Carmen Varela %A Ana Avellón %A Ingrid Friesema %A Vennema, Harry %A Kazim Beebeejaun %A Siew Lin Ngui %A Michael Edelstein %A Alison Smith-Palmer %A Niamh Murphy %A Jonathan Dean %A Mirko Faber %A Jürgen Wenzel %A Mia Kontio %A Luise Müller %A Sofie Elisabeth Midgley %A Lena Sundqvist %A Ederth, Josefine Lundberg %A Anne-Marie Roque-Afonso %A Elisabeth Couturier %A Sofieke Klamer %A Javiera Rebolledo %A Vanessa Suin %A Stephan W Aberle %A Schmid, Daniela %A Rita De Sousa %A Augusto, Gonçalo Figueiredo %A Valeria Alfonsi %A Martina Del Manso %A Anna Rita Ciccaglione %A Mellou, Kassiani %A Christos Hadjichristodoulou %A Alastair Donachie %A Maria-Louise Borg %A Maja Sočan %A Poljak, Mario %A Ettore Severi %K ADOLESCENT %K Adult %K Aged %K Aged, 80 and over %K Child %K Child, Preschool %K Disease Outbreaks %K Europe %K European Union %K Genotype %K Hepatitis A %K hepatitis A virus %K Homosexuality, Male %K Hospitalization %K Humans %K Infant %K Infant, Newborn %K Male %K middle aged %K Risk Factors %K Sexual Behavior %K Spain %K Young adult %X

Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.

%B Euro Surveill %V 23 %8 2018 08 %G eng %N 33 %R 10.2807/1560-7917.ES.2018.23.33.1700641 %0 Journal Article %J J Virol %D 2018 %T Inhibition of MALT1 decreases neuroinflammation and pathogenicity of virulent rabies virus in mice. %A E Kip %A J Staal %A Hermann Tima Giresse %A L Verstrepen %A Marta Romano %A K Lemeire %A Vanessa Suin %A Assia Hamouda %A M Baens %A C Libert %A Kalai, M %A Steven Van Gucht %A Beyaert, R %X

Rabies virus is a neurovirulent RNA virus, which causes about 59000 human deaths each year. Treatment for rabies does not exist due to incomplete understanding of the pathogenesis. MALT1 mediates activation of several immune cell types and is involved in the proliferation and survival of cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, leading to the expression of immunoregulatory genes. Here, we examined the impact of genetic or pharmacological MALT1 inhibition in mice on disease development after infection with the virulent rabies virus strain CVS-11. Morbidity and mortality were significantly delayed in compared to mice, which was associated with a lower viral load, proinflammatory gene expression and infiltration and activation of immune cells in brain. Specific deletion of in T cells also delayed disease development while deletion in myeloid cells, neuronal cells or NK cells had no effect. Disease development was also delayed in mice treated with the MALT1 protease inhibitor mepazine, and in knock-in mice expressing a catalytically inactive MALT1 mutant protein, showing an important role of MALT1 proteolytic activity. The described protective effect of MALT1 inhibition against infection with a virulent rabies virus is the precise opposite of the sensitizing effect of MALT1 inhibition that we previously observed in case of infection with an attenuated rabies virus strain. Together, these data demonstrate that the role of immunoregulatory responses in rabies pathogenicity is dependent on virus virulence, and reveal the potential of MALT1 inhibition for therapeutic intervention. Rabies virus is a neurotropic RNA virus that causes encephalitis and still poses an enormous challenge to animal and public health. Efforts to establish reliable therapeutic strategies have been unsuccessful and are hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular protease that mediates the activation of several innate and adaptive immune cells in response to multiple receptors, and therapeutic MALT1 targeting is believed to be a valid approach for autoimmunity and MALT1-addicted cancers. Here, we study the impact of MALT1 deficiency on brain inflammation and disease development in response to infection of mice with the highly virulent CVS-11 rabies virus. We demonstrate that pharmacological or genetic MALT1 inhibition decreases neuroinflammation and extends the survival of CVS-11 infected mice, providing new insights in the biology of MALT1 and rabies virus infection.

%B J Virol %8 2018 Aug 29 %G eng %R 10.1128/JVI.00720-18 %0 Journal Article %J J Virol %D 2018 %T MALT1 controls attenuated rabies virus by inducing early inflammation and T cell activation in the brain. %A E Kip %A J Staal %A L Verstrepen %A H Tima Giresse %A Sanne Terryn %A Marta Romano %A K Lemeire %A Vanessa Suin %A Assia Hamouda %A Kalai, M %A Beyaert, R %A Steven Van Gucht %K MALT1 %K Rabies %X

MALT1 is involved in the activation of immune responses as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signalling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. While MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus (ERA) and observed increased susceptibility with ERA in MALT1-/- mice. Indeed, following intranasal infection with ERA, wild-type mice developed mild transient clinical signs with recovery at 35 DPI. Interestingly, MALT1-/- mice developed severe disease requiring euthanasia around 17 DPI. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1-/- mice at 10DPI as compared to MALT1+/+ infected mice. At 17 DPI, however, inflammatory cell activation was comparable to the one observed in MALT1+/+ mice. Moreover, MALT1-/- mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain.IMPORTANCE Rabies virus is a neurotropic virus which can infect any mammal. Annually, 59000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular protein involved in innate and adaptive immunity, and an interesting therapeutic target because MALT1-deregulated activity has been associated with autoimmunity and cancers. The role of MALT1 in viral infection is however largely unknown. Here, we study the impact of MALT1 on virus infection in the brain, using the attenuated ERA rabies virus in different models of MALT1 deficient mice. We reveal the importance of MALT1-mediated inflammation and T cell activation to control ERA virus, providing new insights in the biology of MALT1 and rabies virus infection.

%B J Virol %8 2018 Jan 24 %G eng %R 10.1128/JVI.02029-17 %0 Journal Article %J Journal of Zoonotic Diseases and Public Health %D 2017 %T Comparative Tick-Borne Encephalitis (Virus) Surveillance in Belgium 2009-2015: Experiences with Diagnostic Tests, Sentinel Species and Surveillance Designs %A Sophie Roelandt %A Vanessa Suin %A Steven Van Gucht %A Yves Van der Stede %A S. Roels %K Tick-borne encephalitis (virus); Wild boar; Roe deer; Sentinel species; %X

When it is not overtly affecting human beings, the Tick-Borne Encephalitis Flavivirus (TBEV) remains mostly unnoticed during its enzootic cycles within vectors and unaffected animal species. Until recently, Belgium was “presumed” free of this important neuro-pathogenic virus without any scientific substantiation. Nonetheless, Belgium is clearly at risk of Tick-Borne Encephalitis (TBE) emergence

and incursions from endemic zones in the neighboring countries. This comparative review paper describes 5 Belgian veterinary serological studies with enzyme-linked immunosorbent assays and seroneutralisation tests (ELISA/SNT), in which several surveillance schemes were used (active/passive, risk-/laboratory-/range-based) in classic TBE sentinel species (dogs, cattle, roe deer, wild boar). Additionally, passive syndromic surveillance in two medical laboratories resulted in inconclusive medical data. Details are given on the scientists’ experiences with available first/second line diagnostic tests and with the different surveillance methods/survey designs. Each of the veterinary studies clearly demonstrated the presence of TBEV-specific antibodies in Belgian sentinels, sometimes even at high seroneutralisation (SNT) titers, while the medical data remain so far inconclusive, despite positive

reactions of some patients in some TBEV-tests. These results have substantiated our suspicion of TBEV-presence in Belgium from 2010 onwards and have allowed sentinel comparisons based on “suitability criteria”. Furthermore, the studies have highlighted the need for further veterinary validation of commercial ELISA tests in comparison to the gold standard SNT.

%B Journal of Zoonotic Diseases and Public Health %V 1 %8 26/07/2017 %G eng %N 4 %R http://www.imedpub.com/articles/comparative-tickborne-encephalitisvirus-surveillance-in-belgium-20092015experiences-with-diagnostic-tests-sentinelspecies-and-surv.php?aid=19858 %0 Report %D 2017 %T Outbreak report Measles – Belgium Wallonia %A Veronik Hutse %A Vanessa Suin %A Martine Sabbe %A Mendes da Costa,E. %K Belgium %K Measles %K outbreak %K Wallonia %I NA %C Brussels, Belgium %P NA %8 2017 %G eng %M NA %0 Book %B TBE in Belgium %D 2017 %T TBE in Belgium %A Vanessa Suin %A Bernard Brochier %A Steven Van Gucht %A Sophie Roelandt %K Belgium %K TBE %B TBE in Belgium %I Global Health Press Pte Ltd %C Singapore %P 3 %8 2017 %@ 978-981-1903-3 %G eng %9 TBE - The Book %) Dobler, G.; Erber, W.; Schmitt H.J. %R https://id-ea.org/tbe %0 Journal Article %J Infect Ecol Epidemiol %D 2016 %T First TBEV serological screening in Flemish wild boar. %A Sophie Roelandt %A Vanessa Suin %A Yves Van der Stede %A Lamoral, Sophie %A Sylvie Marché %A Marylène Tignon %A Saiz, Juan Carlos %A Escribano-Romero, Estela %A Casaer, Jim %A Bernard Brochier %A Steven Van Gucht %A S. Roels %A Vervaeke, Muriel %X

In the frame of a Flemish wildlife surveillance in 2013, a serological screening was performed on sera from wild boar (Sus scrofa; n=238) in order to detect tick-borne encephalitis virus (TBEV)-specific antibodies. Neutralising antibodies were titrated with a seroneutralisation test (SNT), using two cut-off titres (1/10-1/15). Seven wild boars were found TBEV-seropositive and showed moderate (>1/15) to high (>1/125) SNT-titres; three individuals had borderline results (1/10-1/15). This study demonstrated the presence of TBEV-specific antibodies in wild boar and highlighted potential TBEV-foci in Flanders. Additional surveillance including direct virus testing is now recommended.

%B Infect Ecol Epidemiol %V 6 %P 31099 %8 2016 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/27087689?dopt=Abstract %R 10.3402/iee.v6.31099 %0 Journal Article %J Case Rep Neurol %D 2016 %T New-Onset Refractory Status Epilepticus: More Investigations, More Questions. %A Dillien, Philippe %A Susana Ferrao Santos %A van Pesch, Vincent %A Vanessa Suin %A Lamoral, Sophie %A Hantson, Philippe %K Cryptogenic origin %K Japanese encephalitis virus %K New-onset refractory status epilepticus %K Seronegative limbic encephalitis %K SMC3 gene %X

A 27-year-old previously healthy woman was admitted to the hospital with recurrent seizures. Status epilepticus developed that became refractory to third-line therapy with propofol and barbiturates. The patient had a very extensive diagnostic workup including autoimmune, viral and genetic investigations. A tentative immune therapy was proposed with high doses of steroids and plasma exchanges. Our patient had an inherited heterozygous single nucleotide variant in the sequence c.1280A>G [p.Lys427Arg] of the SMC3 gene that was insufficient to explain the seizures. Surprisingly, IgM antibodies against Japanese encephalitis virus were positive on the serum drawn 11 days after symptom onset, as detected by ELISA and the immunofluorescence antibody (IFA) technique. IgG antibodies were also positive using the IFA technique, but not with ELISA. The same investigations as well as the detection of the viral genome by the q-RT-PCR technique were negative on cerebrospinal fluid. Despite the suspicion of a viral infection, we concluded that our patient had a new-onset refractory status epilepticus of cryptogenic origin. Termination of the status epilepticus was obtained after 47 days, with a possible benefit from the introduction of ketamine.

%B Case Rep Neurol %V 8 %P 127-33 %8 2016 May-Aug %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/27462243?dopt=Abstract %& 127 %R 10.1159/000447295 %0 Report %D 2016 %T Zoönosen en vectoroverdraagbare ziekten. Samenvattend jaaroverzicht 2015 %A Javiera Rebolledo %A Tinne Lernout %A Amber Litzroth %A Dominique Van Beckhoven %A Bernard Brochier %A Delaere, B %A David Fretin %A Hing,M. %A Jacobs,J.A. %A B Kabamba Mukadi %A Marcella Mori %A Patteet,S. %A Saegeman,V. %A Vanessa Suin %A Truyens,C. %A Vanrompay, D %A Van Esbroeck, Marjan %A Steven Van Gucht %A P Wattiau %K 2015 %K Surveillance %K vectoroverdraagbare ziekten %K zoonosen %I WIV-ISP %C Brussel, België %P 17 %8 Okt 2016 %G eng %M D/2016/2505/39 %0 Report %D 2016 %T Zoonoses et maladies à transmission vectorielle. Surveillance épidémiologique en Belgique - Synthèse annuelle 2015 %A Javiera Rebolledo %A Tinne Lernout %A Amber Litzroth %A Dominique Van Beckhoven %A Bernard Brochier %A Delaere,B. %A David Fretin %A Hing,M. %A B Kabamba Mukadi %A Marcella Mori %A Patteet,S. %A Saegeman,V. %A Vanessa Suin %A Truyens,C. %A Vanrompay, D %A Van Esbroeck, Marjan %A Steven Van Gucht %A P Wattiau %K 2015 %K Belgique %K maladies à transmission vectorielle %K Surveillance %K Zoonoses %I WIV-ISP %C Bruxelles, Belgique %P 22 %8 Oct 2016 %G eng %M D/2016/2505/38 %0 Generic %D 2015 %T Arbo-VIRTUESS: Evaluation of the use of non-invasive tests for early screening and survey of arboviruses %A Sylvia Broeders %A Sigrid C.J. De Keersmaecker %A Vanessa Suin %A Steven Van Gucht %A Pol,M. %A Gourinat,A.C. %A Biron,A. %A Dupont-Rouzeyrol,M. %A Vanhomwegen,J. %A Manuguerra,J.C. %A Berlioz-Arthaud,A. %A Enfissi,A. %A Matheus,S %A Rousset,D. %A Nancy Roosens %K Arbo-virtuess %K EVALUATION %K International %K non-invasive %K SCREENING %K survey %K symposium %K Test %K tests %K use %B International Scientific Symposium %I NA %C NA %8 14/10/2015 %G eng %N Institut Pasteur International Network %1 5224 %2 14-16/10/2015 %0 Generic %D 2015 %T Impact of MALT1, an upstream mediator of NF-kB and immune cell activation, on rabies virus disease. %A E Kip %A Vanessa Suin %A J Staal %A Michael Kalai %A Beyaert,R. %A Steven Van Gucht %K Activation %K an %K Cell %K conference %K disease %K Impact %K ON %K Rabies %K Rabies virus %K VIRUS %B RITA conference: Rabies in the Americas %8 0/0/2015 %G eng %N XX %1 37052 %2 4/10/2015;8/10/2015 %0 Conference Proceedings %D 2015 %T Le risque des renards pour la santé publique à Bruxelles %A Vanessa Suin %E T.l. Bruxelles %K Bruxelles %K de %K LE %K santé %K santé publique %8 27/5/2015 %G eng %1 39208 %0 Journal Article %J Infect Ecol Epidemiol %D 2015 %T Serologic screening for 13 infectious agents in roe deer (Capreolus capreolus) in Flanders. %A Tavernier, Paul %A Sys, Stanislas U %A Kris De Clercq %A Ilse De Leeuw %A Ann Brigitte Cay %A Miet De Baere %A Nick De Regge %A David Fretin %A Virginie Roupie %A Govaerts, Marc %A Heyman, Paul %A Vanrompay, Daisy %A Yin, Lizi %A Kalmar, Isabelle %A Vanessa Suin %A Bernard Brochier %A Alexandre Dobly %A Stéphane De Craeye %A Sophie Roelandt %A Goossens, Els %A S. Roels %X

INTRODUCTION: In order to investigate the role of roe deer in the maintenance and transmission of infectious animal and human diseases in Flanders, we conducted a serologic screening in 12 hunting areas.

MATERIALS AND METHODS: Roe deer sera collected between 2008 and 2013 (n=190) were examined for antibodies against 13 infectious agents, using indirect enzyme-linked immunosorbent assay, virus neutralisation, immunofluorescence, or microagglutination test, depending on the agent.

RESULTS AND DISCUSSION: High numbers of seropositives were found for Anaplasma phagocytophilum (45.8%), Toxoplasma gondii (43.2%) and Schmallenberg virus (27.9%), the latter with a distinct temporal distribution pattern following the outbreak in domestic ruminants. Lower antibody prevalence was found for Chlamydia abortus (6.7%), tick-borne encephalitis virus (5.1%), Neospora caninum (4.8%), and Mycobacterium avium subsp paratuberculosis (4.1%). The lowest prevalences were found for Leptospira (1.7%), bovine viral diarrhoea virus 1 (1.3%), and Coxiella burnetii (1.2%). No antibodies were found against Brucella sp., bovine herpesvirus 1, and bluetongue virus. A significant difference in seroprevalence between ages (higher in adults >1 year) was found for N. caninum. Four doubtful reacting sera accounted for a significant difference in seroprevalence between sexes for C. abortus (higher in females).

CONCLUSIONS: Despite the more intensive landscape use in Flanders, the results are consistent with other European studies. Apart from maintaining C. abortus and MAP, roe deer do not seem to play an important role in the epidemiology of the examined zoonotic and domestic animal pathogens. Nevertheless, their meaning as sentinels should not be neglected in the absence of other wild cervid species.

%B Infect Ecol Epidemiol %V 5 %P 29862 %8 2015 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/26609692?dopt=Abstract %R 10.3402/iee.v5.29862 %0 Report %D 2015 %T Zoönosen en Vector-Overdraagbare Ziekten. Epidemiologische surveillance in België, 2013 en 2014 %A Javiera Rebolledo %A Tinne Lernout %A Amber Litzroth %A Dominique Van Beckhoven %A Bernard Brochier %A Delaere,B. %A David Fretin %A Heuninckx,W. %A Hing,M. %A Jacobs, J. %A B Kabamba Mukadi %A Maes,P. %A Marcella Mori %A Patteet,S. %A Sophie Quoilin %A Saegeman,V. %A Vanessa Suin %A Truyens,C. %A Vanrompay, D %A M. Van Esbroeck %A Steven Van Gucht %A P Wattiau %K 2013 %K 2014 %K jaarrapport %K overdraagbare ziekten %K Vector %K zoonosen %I WIV-ISP %C Brussel, België %P 114 %8 Dec 2015 %G eng %M D/2015/2505/74 %0 Report %D 2015 %T Zoonoses et maladies à transmission vectorielle. Surveillance épidémiologique en Belgique, 2013 et 2014 %A Javiera Rebolledo %A Tinne Lernout %A Amber Litzroth %A Dominique Van Beckhoven %A Bernard Brochier %A Delaere,B. %A David Fretin %A Heuninckx,W. %A Hing,M. %A Jacobs,J.A. %A B Kabamba Mukadi %A Maes,P. %A Marcella Mori %A Patteet,S. %A Sophie Quoilin %A Saegeman,V. %A Vanessa Suin %A Truyens,C. %A Vanrompay, D %A Van Esbroeck, Marjan %A Steven Van Gucht %A P Wattiau %K 2013 %K 2014 %K maladies à transmission vectorielle %K Surveillance %K Zoonoses %I WIV-ISP %C Bruxelles, Belgique %P 116 %8 12/2015 %G eng %M D/2015/2505/73 %0 Journal Article %J Vector Borne Zoonotic Dis %D 2014 %T Autochthonous tick-borne encephalitis virus-seropositive cattle in Belgium: a risk-based targeted serological survey. %A Sophie Roelandt %A Vanessa Suin %A Riocreux, Flavien %A Lamoral, Sophie %A Van der Heyden, Sara %A Yves Van der Stede %A Bénédicte Lambrecht %A Ann Brigitte Cay %A Bernard Brochier %A S. Roels %A Steven Van Gucht %K Animals %K Antibodies, Viral %K Arachnid Vectors %K Belgium %K Cattle %K Cattle Diseases %K cross-sectional studies %K Encephalitis Viruses, Tick-Borne %K Encephalitis, Tick-Borne %K Female %K Humans %K Ixodes %K mice %K risk %K Sentinel Surveillance %K Seroepidemiologic Studies %K Zoonoses %X

The risk of tick-borne encephalitis virus (TBEV) introduction into Belgium remains high, and the presence of infected wildlife in Belgium is suspected. Domestic animals can serve as excellent sentinels for TBEV surveillance to install an early warning surveillance component for this emerging zoonotic disease of public health importance. In a targeted, risk-based and cross-sectional sampling design, serological screening was performed on Belgian cattle (n=650), selected from the 2010 Belgian national cattle surveillance serum bank. All samples were subjected to a gold standard TBEV seroneutralization test (SNT), based on the rapid fluorescent focus inhibition test (RFFIT) protocol. Seventeen bovines were seropositive (titer >1/15) and six had borderline results (1/10 < titer < 1/15). The accuracy of the RFFIT-SNT was confirmed in a mouse inoculation test. The overall bovine TBEV seroprevalence in the targeted area was estimated between 2.61% and 4.29%. This confirms for the first time the presence of infected foci in Belgium. Further surveillance in cattle, other sentinels, ticks, and humans at risk is recommended to further determine the location and size of endemic foci and the risk for public health.

%B Vector Borne Zoonotic Dis %V 14 %P 640-7 %8 2014 Sep %G eng %N 9 %1 http://www.ncbi.nlm.nih.gov/pubmed/25229702?dopt=Abstract %R 10.1089/vbz.2014.1576 %0 Government Document %D 2014 %T Connaissez-vous le virus de l'encéphalite à tiques?36937 %A Vanessa Suin %A Bernard Brochier %K de %K LE %K VIRUS %X NA %B Médisphère %V 451 %8 19/8/2014 %G eng %1 39206 %0 Generic %D 2014 %T ORIENT-EXPRESS in times of crisis %A Sylvia Broeders %A Sigrid C.J. De Keersmaecker %A Steven Van Gucht %A Isabelle Thomas %A Vanessa Suin %A Katelijne Dierick %A N Botteldoorn %A Steven Van Borm %A Nancy Roosens %K application %K applications %K arbovirus %K crisis %K detection %K gasto-intestinal parasites %K GMO %K health %K Luminex %K NGS %K public %K public health %K Public-health %K qPCR %K time %K Times %B Applications of Next Generation Sequencing for public health %I NA %C NA %8 0/0/2014 %G eng %N WIV-ISP %1 4873 %2 10/10/2014 %0 Journal Article %J Biomed Res Int %D 2014 %T A two-step lyssavirus real-time polymerase chain reaction using degenerate primers with superior sensitivity to the fluorescent antigen test. %A Vanessa Suin %A Nazé, Florence %A Aurélie Francart %A Lamoral, Sophie %A Stéphane De Craeye %A Kalai, Michael %A Steven Van Gucht %K Animals %K Base Sequence %K brain %K Cats %K Chiroptera %K Computer Simulation %K Dogs %K Fluorescent Antibody Technique %K Humans %K Limit of Detection %K Lyssavirus %K mice %K Molecular Sequence Data %K Real-Time Polymerase Chain Reaction %K Reproducibility of Results %K Reverse Transcriptase Polymerase Chain Reaction %K Rhabdoviridae Infections %K RNA, Viral %K Sequence Alignment %X

A generic two-step lyssavirus real-time reverse transcriptase polymerase chain reaction (qRT-PCR), based on a nested PCR strategy, was validated for the detection of different lyssavirus species. Primers with 17 to 30% of degenerate bases were used in both consecutive steps. The assay could accurately detect RABV, LBV, MOKV, DUVV, EBLV-1, EBLV-2, and ABLV. In silico sequence alignment showed a functional match with the remaining lyssavirus species. The diagnostic specificity was 100% and the sensitivity proved to be superior to that of the fluorescent antigen test. The limit of detection was ≤ 1 50% tissue culture infectious dose. The related vesicular stomatitis virus was not recognized, confirming the selectivity for lyssaviruses. The assay was applied to follow the evolution of rabies virus infection in the brain of mice from 0 to 10 days after intranasal inoculation. The obtained RNA curve corresponded well with the curves obtained by a one-step monospecific RABV-qRT-PCR, the fluorescent antigen test, and virus titration. Despite the presence of degenerate bases, the assay proved to be highly sensitive, specific, and reproducible.

%B Biomed Res Int %V 2014 %P 256175 %8 2014 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/24822188?dopt=Abstract %R 10.1155/2014/256175 %0 Journal Article %J Acta Clin Belg %D 2013 %T Favourable outcome in a patient bitten by a rabid bat infected with the European bat lyssavirus-1. %A Steven Van Gucht %A Verlinde, R %A Colyn, J %A Jean Vanderpas %A Vanhoof, R %A S. Roels %A Francart, A %A Bernard Brochier %A Vanessa Suin %K Animals %K Belgium %K Bites and Stings %K Chiroptera %K Cross Protection %K Europe %K Genotype %K Humans %K Lyssavirus %K Male %K Post-Exposure Prophylaxis %K Rabies %K Rabies Vaccines %K Rhabdoviridae Infections %K Treatment Outcome %K Vaccination %X

The classic rabies virus (genotype 1) has been eliminated in Western Europe, but related lyssaviruses still circulate in local bats. In August 2010, a Belgian photographer was bitten upon provocation of a disoriented Eptesicus serotinus bat in Spain. The bat was infected with European bat lyssavirus-1 (genotype 5). The isolate proved highly neurovirulent in mice. The patient had received preventive rabies immunisations years before the incident and received two boosters with the HDCV rabies vaccine afterwards. Available vaccines are based on the classic rabies virus, which is significantly divergent from the European bat lyssavirus-1. Fortunately, the patient's serological immune response demonstrated satisfactory neutralisation of the 2010 EBLV-1 isolate, using an intracerebral challenge model in mice. Most likely, the patient's life was saved thanks to vaccination with the classic rabies vaccine, which proved sufficiently protective against European bat lyssavirus-1. This case highlights the need for preventive rabies vaccination in people, who come in contact with bats and to seek medical council after a scratch or bite from a bat.

%B Acta Clin Belg %V 68 %P 54-8 %8 2013 Jan-Feb %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/23627196?dopt=Abstract %R 10.2143/ACB.68.1.2062721 %0 Report %D 2013 %T Favourable outcome of a bite incident by a rabid bat infected with the European bat lyssavirus-1 %A Steven Van Gucht %A Colyn,J. %A Jean Vanderpas %A R. Vanhoof %A A. Francart %A Bernard Brochier %A Vanessa Suin %K a %K bat %K bite %K European %K incident %K Lyssavirus %K outcome %I WIV-ISP %C Brussels %P - %8 0/0/2013 %G eng %1 38420 %0 Journal Article %J Microbes Infect %D 2013 %T Infectivity of rabies virus-exposed macrophages. %A Nazé, Florence %A Vanessa Suin %A Lamoral, Sophie %A Aurélie Francart %A Bernard Brochier %A S. Roels %A Jan Mast %A Kalai, Michael %A Steven Van Gucht %K Animals %K Antibodies, Neutralizing %K Antibodies, Viral %K Antibody Formation %K Antigens, Viral %K Bone Marrow %K brain %K Cell Death %K Immunity, Humoral %K Injections, Intramuscular %K Macrophages %K mice %K Mice, Inbred C57BL %K Microscopy, Electron %K Nose %K Rabies %K Rabies virus %K RNA, Viral %K Spleen %K Viral Load %K Virus Cultivation %X

Rabies virus distributes widely in infected mice, including lymphoid tissues and spleen macrophages. The infection characteristics in murine macrophages and the infectivity of virus-exposed macrophages were examined upon inoculation in mice. In vitro, Mf4/4 spleen macrophages supported mild virus production (10(4)-fold less than neuroblastoma), with formation of typical virions. Bone marrow-derived macrophages (BMM) were most efficient to capture virus, but new virus production was not detected. Virus-induced cell death was significantly stronger in BMM, which might have eliminated BMM with productive infection. Still, viral RNA remained detectable in the remaining BMM for at least 4 weeks. Injection of in vitro-infected Mf4/4 in the nose or brain proved efficient to propagate infection in mice, even when cells were pre-incubated with neutralizing antibodies. Surprisingly, injection of ex-vivo-infected BMM in the brain also led to lethal infection in 8 out of 12 mice. Injection of infected Mf4/4 in the muscle mostly favoured a protective antibody response. Despite that macrophages are less fit to support virus production, they can still act as a source of infectious virus upon transfer in mice. This may be relevant for screening donor organs/cells, for which RT-PCR should be preferred over the traditional antigen or virus isolation assays.

%B Microbes Infect %V 15 %P 115-25 %8 2013 Feb %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/23159243?dopt=Abstract %R 10.1016/j.micinf.2012.10.018 %0 Generic %D 2013 %T Tick-borne encephalitis virus - seropositive cattle in Belgium: a risk-based screening for (TBEV) antibodies in bovine sera %A Sophie Roelandt %A Vanessa Suin %A Riocreux,F. %A S. Lamoral %A Yves Van der Stede %A Steven Van Gucht %A Bernard Brochier %A S. Roels %E Technical University of Denmark %K a %K antibodies %K Antibody %K association %K Belgium %K Cattle %K conference %K International %K SCREENING %K serum %K TBEV %K VIRUS %B MedVetNet Association International Scientific Conference 2013 %P 49 - 49 %8 24/6/2013 %G eng %N Technical University of Denmark %1 38336 %2 24-25/06/2013 %& 49 %0 Generic %D 2013 %T Tick-borne encephalitis virus (TBEV) - Seroprevalence study for TBEV antibodies in bovine sera in Belgium: a risk-based screening %A Vanessa Suin %A Sophie Roelandt %A S. Lamoral %A Riocreux,F. %A Yves Van der Stede %A Bernard Brochier %A S. Roels %A Steven Van Gucht %K a %K antibodies %K Antibody %K Belgium %K SCREENING %K serum %K study %K TBEV %K VIRUS %B Epizone %I NA %C NA %8 0/10/2013 %G eng %N Epizone %1 38361 %2 October 2013 %0 Report %D 2012 %T An intranasal infection model of rabies to study disease mechanisms and therapies of viral encephalitis %A Vanessa Suin %A Rosseels,V. %A Naze,F. %A A. Francart %A S. Lamoral %A Michael Kalai %A Steven Van Gucht %K an %K disease %K INFECTION %K mechanism %K mechanisms %K MODEL %K Rabies %K study %K Therapy %I WIV-ISP %C Brussels %P - %8 0/0/2012 %G eng %1 285 %0 Journal Article %J Cell Death Differ %D 2007 %T The caspase-generated fragments of PKR cooperate to activate full-length PKR and inhibit translation. %A Kalai, M %A Vanessa Suin %A Festjens, N %A Meeus, A %A Bernis, A %A Wang, X-M %A Saelens, X %A Vandenabeele, P %K Apoptosis %K Caspase Inhibitors %K caspases %K Cell Line %K eIF-2 Kinase %K Enzyme Activation %K Enzyme Inhibitors %K Humans %K Immunoprecipitation %K Jurkat Cells %K Necrosis %K Peptide Fragments %K Phosphorylation %K Protein Binding %K Protein Biosynthesis %K Protein Processing, Post-Translational %K Protein Structure, Tertiary %K Receptor-Interacting Protein Serine-Threonine Kinases %K RNA, Double-Stranded %K Signal Transduction %X

We have studied the involvement of receptor interacting protein kinase-1 (RIP1) and dsRNA-activated protein kinase (PKR) in external dsRNA-induced apoptotic and necrotic cell death in Jurkat T cell lymphoma. Our results suggest that RIP1 plays an imported role in dsRNA-induced apoptosis and necrosis. We demonstrated that contrary to necrosis, protein synthesis is inhibited in apoptosis. Here, we show that phosphorylation of translation initiation factor 2-alpha (eukaryotic initiation factor 2-alpha (eIF2-alpha)) and its kinase, PKR, occur in dsRNA-induced apoptosis but not in necrosis. These events are caspase-dependent and coincide with the appearance of the caspase-mediated PKR fragments, N-terminal domain (ND) and kinase domain (KD). Our immunoprecipitation experiments demonstrated that both fragments could independently co-precipitate with full-length PKR. Expression of PKR-KD leads to PKR and eIF2-alpha phosphorylation and inhibits protein translation, whereas that of PKR-ND does not. Co-expression of PKR-ND and PKR-KD promotes their interaction with PKR, PKR and eIF2-alpha phosphorylation and suppresses protein translation better than PKR-KD alone. Our findings suggest a caspase-dependent mode of activation of PKR in apoptosis in which the PKR-KD fragment interacts with and activates intact PKR. PKR-ND facilitates the interaction of PKR-KD with full-length PKR and thus the activation of the kinase and amplifies the translation inhibitory signal.

%B Cell Death Differ %V 14 %P 1050-9 %8 2007 May %G eng %N 5 %1 http://www.ncbi.nlm.nih.gov/pubmed/17318221?dopt=Abstract %R 10.1038/sj.cdd.4402110