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Dr. Anne Goffard
Molecular and Cellular Virology team, Center for Infection and Immunity of Lille (CIIL) Inserm U1019, CNRS UMR 9017, Univ.

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0 Molecular Epidemiology
0 viral entry
0 High throughput sequencing
0 CoronaVirus
0 N-glycans

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Envelope glycoproteins
N-glycans
CoronaVirus
viral entry

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Journal article
Published: 16 November 2019 in Journal of Clinical Virology
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While respiratory viral infections are recognized as a frequent cause of illness in hematopoietic stem cell transplantation (HSCT) recipients, HCoV−OC43 infections have rarely been investigated as healthcare-associated infections in this population. In this report, HCoV−OC43 isolates collected from HSCT patients were retrospectively characterized to identify potential clusters of infection that may stand for a hospital transmission. Whole-genome and S gene sequences were obtained from nasal swabs using next-generation sequencing and phylogenetic trees were constructed. Similar identity matrix and determination of the most common ancestor were used to compare clusters of patient’s sequences. Amino acids substitutions were analysed. Genotypes B, E, F and G were identified. Two clusters of patients were defined from chronological data and phylogenetic trees. Analyses of amino acids substitutions of the S protein sequences identified substitutions specific for genotype F strains circulating among European people. HCoV−OC43 may be implicated in healthcare-associated infections.

ACS Style

Delphine Beury; Léa Fléchon; Florence Maurier; Ségolène Caboche; Jean-Stéphane Varré; Hélène Touzet; Karine Faure; Jean Dubuisson; David Hot; Benoit Guery; Anne Goffard. Use of whole-genome sequencing in the molecular investigation of care-associated HCoV-OC43 infections in a hematopoietic stem cell transplant unit. Journal of Clinical Virology 2019, 122, 104206 -104206.

AMA Style

Delphine Beury, Léa Fléchon, Florence Maurier, Ségolène Caboche, Jean-Stéphane Varré, Hélène Touzet, Karine Faure, Jean Dubuisson, David Hot, Benoit Guery, Anne Goffard. Use of whole-genome sequencing in the molecular investigation of care-associated HCoV-OC43 infections in a hematopoietic stem cell transplant unit. Journal of Clinical Virology. 2019; 122 ():104206-104206.

Chicago/Turabian Style

Delphine Beury; Léa Fléchon; Florence Maurier; Ségolène Caboche; Jean-Stéphane Varré; Hélène Touzet; Karine Faure; Jean Dubuisson; David Hot; Benoit Guery; Anne Goffard. 2019. "Use of whole-genome sequencing in the molecular investigation of care-associated HCoV-OC43 infections in a hematopoietic stem cell transplant unit." Journal of Clinical Virology 122, no. : 104206-104206.

Journal article
Published: 01 September 2019 in Journal of Biological Chemistry
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Coronavirus M proteins represent the major protein component of the viral envelope. They play an essential role during viral assembly by interacting with all of the other structural proteins. Coronaviruses bud into the endoplasmic reticulum (ER)–Golgi intermediate compartment (ERGIC), but the mechanisms by which M proteins are transported from their site of synthesis, the ER, to the budding site remain poorly understood. Here, we investigated the intracellular trafficking of the Middle East respiratory syndrome coronavirus (MERS-CoV) M protein. Subcellular localization analyses revealed that the MERS-CoV M protein is retained intracellularly in the trans-Golgi network (TGN), and we identified two motifs in the distal part of the C-terminal domain as being important for this specific localization. We identified the first motif as a functional diacidic DxE ER export signal, because substituting Asp-211 and Glu-213 with alanine induced retention of the MERS-CoV M in the ER. The second motif, 199KxGxYR204, was responsible for retaining the M protein in the TGN. Substitution of this motif resulted in MERS-CoV M leakage toward the plasma membrane. We further confirmed the role of 199KxGxYR204 as a TGN retention signal by using chimeras between MERS-CoV M and the M protein of infectious bronchitis virus (IBV). Our results indicated that the C-terminal domains of both proteins determine their specific localization, namely TGN and ERGIC/cis-Golgi for MERS-M and IBV-M, respectively. Our findings indicate that MERS-CoV M protein localizes to the TGN because of the combined presence of an ER export signal and a TGN retention motif.

ACS Style

Anabelle Perrier; Ariane Bonnin; Lowiese Desmarets; Adeline Danneels; Anne Goffard; Yves Rouillé; Jean Dubuisson; Sandrine Belouzard. The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal. Journal of Biological Chemistry 2019, 294, 14406 -14421.

AMA Style

Anabelle Perrier, Ariane Bonnin, Lowiese Desmarets, Adeline Danneels, Anne Goffard, Yves Rouillé, Jean Dubuisson, Sandrine Belouzard. The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal. Journal of Biological Chemistry. 2019; 294 (39):14406-14421.

Chicago/Turabian Style

Anabelle Perrier; Ariane Bonnin; Lowiese Desmarets; Adeline Danneels; Anne Goffard; Yves Rouillé; Jean Dubuisson; Sandrine Belouzard. 2019. "The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal." Journal of Biological Chemistry 294, no. 39: 14406-14421.

Journal article
Published: 11 April 2019 in JMIR Medical Education
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During their studies, pharmacy students must acquire the specific skills in clinical virology required for their subsequent professional practice. Recent experiments on teaching and learning in higher education have shown that hybrid courses strengthen the students' commitment to learning and enable high-quality knowledge acquisition. This study concerned the design and deployment of a hybrid course that combines face-to-face and Web-based instruction in clinical virology for fourth-year pharmacy students. The study's objectives were to (1) measure the students' level of involvement in the course, (2) gauge their interest in this type of learning, and (3) highlight any associated difficulties. The study included 194 fourth-year pharmacy students from the Lille Faculty of Pharmacy (University of Lille, Lille, France) between January and June 2017. The students followed a hybrid course comprising an online learning module and 5 tutorial sessions in which professional situations were simulated. The learning module and 3 online evaluation sessions were delivered via the Moodle learning management system. Each tutorial session ended with an evaluation. The number of Moodle log-ins, the number of views of learning resources, and the evaluation marks were recorded. The coefficient for the correlation between the marks in the online evaluation and those in the tutorials was calculated. The students' opinions and level of satisfaction were evaluated via a course questionnaire. The course's learning resources and Web pages were viewed 21,446 and 3413 times, respectively. Of the 194 students, 188 (96.9%) passed the course (ie, marks of at least 10 out of 20). There was a satisfactory correlation between the marks obtained in the online evaluations and those obtained after the tutorials. The course met the students' expectations in 53.2% of cases, and 57.4% of the students stated that they were able to work at their own pace. Finally, 26.6% of the students stated that they had difficulty organizing their work around this hybrid course. Our results showed that pharmacy students were strongly in favor of a hybrid course. The levels of attendance and participation were high. However, teachers must be aware that some students will encounter organizational difficulties.

ACS Style

Anne Goffard; Pascal Odou; El Moukhtar Aliouat; Cécile-Marie Aliouat-Denis; Christophe Carnoy; Bertrand Décaudin; Cuny Damien; Mounira Hamoudi; Claire Pinçon; Katia Quelennec; Sébastien Zanetti; Pierre Ravaux; Annie Standaert; Ramez Alkoudmani; Sandra Barteit; Caroline Perrin. Development and Evaluation of a Hybrid Course in Clinical Virology at a Faculty of Pharmacy in Lille, France. JMIR Medical Education 2019, 5, e10766 .

AMA Style

Anne Goffard, Pascal Odou, El Moukhtar Aliouat, Cécile-Marie Aliouat-Denis, Christophe Carnoy, Bertrand Décaudin, Cuny Damien, Mounira Hamoudi, Claire Pinçon, Katia Quelennec, Sébastien Zanetti, Pierre Ravaux, Annie Standaert, Ramez Alkoudmani, Sandra Barteit, Caroline Perrin. Development and Evaluation of a Hybrid Course in Clinical Virology at a Faculty of Pharmacy in Lille, France. JMIR Medical Education. 2019; 5 (1):e10766.

Chicago/Turabian Style

Anne Goffard; Pascal Odou; El Moukhtar Aliouat; Cécile-Marie Aliouat-Denis; Christophe Carnoy; Bertrand Décaudin; Cuny Damien; Mounira Hamoudi; Claire Pinçon; Katia Quelennec; Sébastien Zanetti; Pierre Ravaux; Annie Standaert; Ramez Alkoudmani; Sandra Barteit; Caroline Perrin. 2019. "Development and Evaluation of a Hybrid Course in Clinical Virology at a Faculty of Pharmacy in Lille, France." JMIR Medical Education 5, no. 1: e10766.

Preprint
Published: 12 April 2018
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BACKGROUND During their studies, pharmacy students must acquire the specific skills in clinical virology required for their subsequent professional practice. Recent experiments on teaching and learning in higher education have shown that hybrid courses strengthen the students’ commitment to learning and enable high-quality knowledge acquisition. OBJECTIVE This study concerned the design and deployment of a hybrid course that combines face-to-face and Web-based instruction in clinical virology for fourth-year pharmacy students. The study’s objectives were to (1) measure the students’ level of involvement in the course, (2) gauge their interest in this type of learning, and (3) highlight any associated difficulties. METHODS The study included 194 fourth-year pharmacy students from the Lille Faculty of Pharmacy (University of Lille, Lille, France) between January and June 2017. The students followed a hybrid course comprising an online learning module and 5 tutorial sessions in which professional situations were simulated. The learning module and 3 online evaluation sessions were delivered via the Moodle learning management system. Each tutorial session ended with an evaluation. The number of Moodle log-ins, the number of views of learning resources, and the evaluation marks were recorded. The coefficient for the correlation between the marks in the online evaluation and those in the tutorials was calculated. The students’ opinions and level of satisfaction were evaluated via a course questionnaire. RESULTS The course’s learning resources and Web pages were viewed 21,446 and 3413 times, respectively. Of the 194 students, 188 (96.9%) passed the course (ie, marks of at least 10 out of 20). There was a satisfactory correlation between the marks obtained in the online evaluations and those obtained after the tutorials. The course met the students’ expectations in 53.2% of cases, and 57.4% of the students stated that they were able to work at their own pace. Finally, 26.6% of the students stated that they had difficulty organizing their work around this hybrid course. CONCLUSIONS Our results showed that pharmacy students were strongly in favor of a hybrid course. The levels of attendance and participation were high. However, teachers must be aware that some students will encounter organizational difficulties.

ACS Style

Anne Goffard; Pascal Odou; El Moukhtar Aliouat; Cécile-Marie Aliouat-Denis; Christophe Carnoy; Bertrand Décaudin; Cuny Damien; Mounira Hamoudi; Claire Pinçon; Katia Quelennec; Sébastien Zanetti; Pierre Ravaux; Annie Standaert; Damien Cuny. Development and Evaluation of a Hybrid Course in Clinical Virology at a Faculty of Pharmacy in Lille, France (Preprint). 2018, 1 .

AMA Style

Anne Goffard, Pascal Odou, El Moukhtar Aliouat, Cécile-Marie Aliouat-Denis, Christophe Carnoy, Bertrand Décaudin, Cuny Damien, Mounira Hamoudi, Claire Pinçon, Katia Quelennec, Sébastien Zanetti, Pierre Ravaux, Annie Standaert, Damien Cuny. Development and Evaluation of a Hybrid Course in Clinical Virology at a Faculty of Pharmacy in Lille, France (Preprint). . 2018; ():1.

Chicago/Turabian Style

Anne Goffard; Pascal Odou; El Moukhtar Aliouat; Cécile-Marie Aliouat-Denis; Christophe Carnoy; Bertrand Décaudin; Cuny Damien; Mounira Hamoudi; Claire Pinçon; Katia Quelennec; Sébastien Zanetti; Pierre Ravaux; Annie Standaert; Damien Cuny. 2018. "Development and Evaluation of a Hybrid Course in Clinical Virology at a Faculty of Pharmacy in Lille, France (Preprint)." , no. : 1.

Journal article
Published: 01 January 2018 in Gastroenterology
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Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. Approximately 2 billion people live in areas endemic for HEV and are at risk of infection. The HEV genome encodes 3 proteins, including the ORF2 capsid protein. Detailed analyses of the HEV lifecycle has been hampered by the lack of an efficient viral culture system.We performed studies with gt3 HEV cell culture-produced particles (HEVcc) and patient blood and stool samples. Samples were fractionated on iodixanol gradients and cushions. Infectivity assays were performed in vitro and in human liver chimeric mice. Proteins were analyzed by biochemical and proteomic approaches. Infectious particles were analyzed by transmission electron microscopy. HEV antigen levels were measured with the Wantaï ELISA.We developed an efficient cell culture system and isolated HEV particles that were infectious in vitro and in vivo. Using transmission electron microscopy, we defined the ultrastructure of HEVcc and particles from patient sera and stool samples. We also identified the precise sequence of the infectious particle-associated ORF2 capsid protein. In cultured cells and in samples from patients, HEV produced 3 forms of the ORF2 capsid protein: infectious/intracellular ORF2 (ORF2i), glycosylated ORF2 (ORF2g), and cleaved ORF2 (ORF2c). The ORF2i protein associated with infectious particles, whereas the ORF2g and ORF2c proteins were massively secreted glycoproteins not associated with infectious particles. ORF2g and ORF2c were the most abundant antigens detected in sera from patients.We developed a cell culture system and characterized HEV particles; we identified 3 ORF2 capsid proteins (ORF2i, ORF2g, and ORFc). These findings will advance our understanding of the HEV lifecycle and improve diagnosis.

ACS Style

Claire Montpellier; Czeslaw Wychowski; Ibrahim M. Sayed; Jean-Christophe Meunier; Jean-Michel Saliou; Maliki Ankavay; Anne Bull; André Pillez; Florence Abravanel; Francois Helle; Etienne Brochot; Hervé Drobecq; Rayan Farhat; Cécile-Marie Aliouat-Denis; Juliano G. Haddad; Jacques Izopet; Philip Meuleman; Anne Goffard; Jean Dubuisson; Laurence Cocquerel. Hepatitis E Virus Lifecycle and Identification of 3 Forms of the ORF2 Capsid Protein. Gastroenterology 2018, 154, 211 -223.e8.

AMA Style

Claire Montpellier, Czeslaw Wychowski, Ibrahim M. Sayed, Jean-Christophe Meunier, Jean-Michel Saliou, Maliki Ankavay, Anne Bull, André Pillez, Florence Abravanel, Francois Helle, Etienne Brochot, Hervé Drobecq, Rayan Farhat, Cécile-Marie Aliouat-Denis, Juliano G. Haddad, Jacques Izopet, Philip Meuleman, Anne Goffard, Jean Dubuisson, Laurence Cocquerel. Hepatitis E Virus Lifecycle and Identification of 3 Forms of the ORF2 Capsid Protein. Gastroenterology. 2018; 154 (1):211-223.e8.

Chicago/Turabian Style

Claire Montpellier; Czeslaw Wychowski; Ibrahim M. Sayed; Jean-Christophe Meunier; Jean-Michel Saliou; Maliki Ankavay; Anne Bull; André Pillez; Florence Abravanel; Francois Helle; Etienne Brochot; Hervé Drobecq; Rayan Farhat; Cécile-Marie Aliouat-Denis; Juliano G. Haddad; Jacques Izopet; Philip Meuleman; Anne Goffard; Jean Dubuisson; Laurence Cocquerel. 2018. "Hepatitis E Virus Lifecycle and Identification of 3 Forms of the ORF2 Capsid Protein." Gastroenterology 154, no. 1: 211-223.e8.

Comparative study
Published: 01 December 2017 in Journal of Virological Methods
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Three molecular assays (FTD® Viral GE from Fast-track diagnostics, RIDA®GENE VSP1 from R-Biopharm, and Xpert Norovirus from Cepheid) were compared for virus detection in acute diarrhea samples. RIDA®GENE and FTD® Viral GE showed perfect/almost perfect agreement for Rotavirus, Sapovirus and Norovirus, substantial agreement for Adenovirus, and moderate agreement for Astrovirus.

ACS Style

Haciba Moudjahed; Claire Pinçon; Kazali Alidjinou; Anny Dewilde; Anne Goffard. Comparison of three molecular assays for detection of enteric viruses in stool samples. Journal of Virological Methods 2017, 250, 55 -58.

AMA Style

Haciba Moudjahed, Claire Pinçon, Kazali Alidjinou, Anny Dewilde, Anne Goffard. Comparison of three molecular assays for detection of enteric viruses in stool samples. Journal of Virological Methods. 2017; 250 ():55-58.

Chicago/Turabian Style

Haciba Moudjahed; Claire Pinçon; Kazali Alidjinou; Anny Dewilde; Anne Goffard. 2017. "Comparison of three molecular assays for detection of enteric viruses in stool samples." Journal of Virological Methods 250, no. : 55-58.

Journal article
Published: 02 December 2015 in Viruses
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Bats are a reservoir for a diverse range of viruses, including coronaviruses (CoVs). To determine the presence of CoVs in French bats, fecal samples were collected between July and August of 2014 from four bat species in seven different locations around the city of Bourges in France. We present for the first time the presence of alpha-CoVs in French Pipistrellus pipistrellus bat species with an estimated prevalence of 4.2%. Based on the analysis of a fragment of the RNA-dependent RNA polymerase (RdRp) gene, phylogenetic analyses show that alpha-CoVs sequences detected in French bats are closely related to other European bat alpha-CoVs. Phylogeographic analyses of RdRp sequences show that several CoVs strains circulate in European bats: (i) old strains detected that have probably diverged a long time ago and are detected in different bat subspecies; (ii) strains detected in Myotis and Pipistrellus bat species that have more recently diverged. Our findings support previous observations describing the complexity of the detected CoVs in bats worldwide.

ACS Style

Anne Goffard; Christine Demanche; Laurent Arthur; Claire Pinçon; Johan Michaux; Jean Dubuisson. Alphacoronaviruses Detected in French Bats Are Phylogeographically Linked to Coronaviruses of European Bats. Viruses 2015, 7, 6279 -6290.

AMA Style

Anne Goffard, Christine Demanche, Laurent Arthur, Claire Pinçon, Johan Michaux, Jean Dubuisson. Alphacoronaviruses Detected in French Bats Are Phylogeographically Linked to Coronaviruses of European Bats. Viruses. 2015; 7 (12):6279-6290.

Chicago/Turabian Style

Anne Goffard; Christine Demanche; Laurent Arthur; Claire Pinçon; Johan Michaux; Jean Dubuisson. 2015. "Alphacoronaviruses Detected in French Bats Are Phylogeographically Linked to Coronaviruses of European Bats." Viruses 7, no. 12: 6279-6290.

Journal article
Published: 13 November 2015 in Philosophy, Ethics, and Humanities in Medicine
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Given that advances in research continuously raise new ethical issues, a multidisciplinary working group of investigators involved in biomedical research has gathered to discuss and compare ethical viewpoints in their daily practice. The working group has drafted a Charter for Ethics in Biomedical Research that encompasses all the steps in the research process, i.e. from the initial idea to analysis and publication of the results. Based on key principles for ethically responsible research, the Charter may serve as a tool for performing research, discussing research issues and training researchers. The Charter should stimulate researchers to think about their responsibility for research in a progressive, caring society.

ACS Style

Sylvie Vandoolaeghe; the “ethic and research” working group; Alessandra Blaizot; Danie Boudiguet; Valerie Bougault; Eduardo Dei Cas; Benoit Foligne; Anne Goffard; Hélène Lefranc; Bénédicte Oxombre; Thomas Trentesaux; Bernard Vandenbunder; Isabelle Wolowczuk; Laurence Delhaes. A charter for biomedical research ethics in a progressive, caring society. Philosophy, Ethics, and Humanities in Medicine 2015, 10, 1 -6.

AMA Style

Sylvie Vandoolaeghe, the “ethic and research” working group, Alessandra Blaizot, Danie Boudiguet, Valerie Bougault, Eduardo Dei Cas, Benoit Foligne, Anne Goffard, Hélène Lefranc, Bénédicte Oxombre, Thomas Trentesaux, Bernard Vandenbunder, Isabelle Wolowczuk, Laurence Delhaes. A charter for biomedical research ethics in a progressive, caring society. Philosophy, Ethics, and Humanities in Medicine. 2015; 10 (1):1-6.

Chicago/Turabian Style

Sylvie Vandoolaeghe; the “ethic and research” working group; Alessandra Blaizot; Danie Boudiguet; Valerie Bougault; Eduardo Dei Cas; Benoit Foligne; Anne Goffard; Hélène Lefranc; Bénédicte Oxombre; Thomas Trentesaux; Bernard Vandenbunder; Isabelle Wolowczuk; Laurence Delhaes. 2015. "A charter for biomedical research ethics in a progressive, caring society." Philosophy, Ethics, and Humanities in Medicine 10, no. 1: 1-6.

Journal article
Published: 25 February 2014 in Journal of Clinical Virology
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Few studies have suggested the potential role of respiratory viruses in cystic fibrosis (CF) exacerbation, but their real impact is probably underestimated. Sixty-four sputum samples collected from 46 adult patients were included in the study: 33 samples were collected during exacerbation of CF, and 31 during the stable phase. After extraction, nucleic acids were tested for the presence of respiratory viruses. When rhinovirus (HRV) was detected, the 5′UTR and VP4/2 regions were sequenced, and phylogenetically analyzed. The characteristics of patients in exacerbation and stable phase were compared. Viruses were found in 25% of samples. The HRV viruses were the most frequently detected followed by coronaviruses. Only the HRV detection was significantly associated with the occurrence of CF pulmonary exacerbation (p < 0.027). Characterization of 5′UTR and VP4/2 regions of the HRV genome specified that HRV-A, -B, -C were detected. All HRV-C were recombinant HRV-Ca. HRV were the most frequently detected viruses; their detection was significantly associated with the occurrence of an exacerbation. The reality of viral recombination between HRV was demonstrated in CF patients for the first time, raising the role of viruses in lung microbiota. Further studies are now warranted to decipher virus impact in CF.

ACS Style

Anne Goffard; Valérie Lambert; Julia Salleron; Stéphanie Herwegh; Ilka Engelmann; Claudine Pinel; Isabelle Pin; Thierry Perrez; Anne Prévotat; Anny Dewilde; Laurence Delhaes. Virus and cystic fibrosis: Rhinoviruses are associated with exacerbations in adult patients. Journal of Clinical Virology 2014, 60, 147 -153.

AMA Style

Anne Goffard, Valérie Lambert, Julia Salleron, Stéphanie Herwegh, Ilka Engelmann, Claudine Pinel, Isabelle Pin, Thierry Perrez, Anne Prévotat, Anny Dewilde, Laurence Delhaes. Virus and cystic fibrosis: Rhinoviruses are associated with exacerbations in adult patients. Journal of Clinical Virology. 2014; 60 (2):147-153.

Chicago/Turabian Style

Anne Goffard; Valérie Lambert; Julia Salleron; Stéphanie Herwegh; Ilka Engelmann; Claudine Pinel; Isabelle Pin; Thierry Perrez; Anne Prévotat; Anny Dewilde; Laurence Delhaes. 2014. "Virus and cystic fibrosis: Rhinoviruses are associated with exacerbations in adult patients." Journal of Clinical Virology 60, no. 2: 147-153.

Case reports
Published: 16 January 2014 in BMJ Case Reports
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This paper presents a case of community-acquired necrotising pneumonia due to Panton-Valentine leukocidine-positive methicillin-susceptible Staphylococcus aureus and A/H1N12009 influenzavirus co-infection in a 26-year-old woman. Despite the presence of pejorative prognostic factors, the clinical course of the patient was favourable.

ACS Style

Karena Riedweg-Moreno; Frederic Wallet; Caroline Blazejewski; Anne Goffard. Successful management of Panton-Valentine leukocidine-positive necrotising pneumonia and A/H1N12009 influenzavirus coinfection in adult. BMJ Case Reports 2014, 2014, 1 .

AMA Style

Karena Riedweg-Moreno, Frederic Wallet, Caroline Blazejewski, Anne Goffard. Successful management of Panton-Valentine leukocidine-positive necrotising pneumonia and A/H1N12009 influenzavirus coinfection in adult. BMJ Case Reports. 2014; 2014 (jan16 1):1.

Chicago/Turabian Style

Karena Riedweg-Moreno; Frederic Wallet; Caroline Blazejewski; Anne Goffard. 2014. "Successful management of Panton-Valentine leukocidine-positive necrotising pneumonia and A/H1N12009 influenzavirus coinfection in adult." BMJ Case Reports 2014, no. jan16 1: 1.

Case reports
Published: 30 May 2013 in The Lancet
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Summary Background Human infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital. Methods Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV. Findings Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9–12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure. Interpretation Patients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor. Funding French Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.

ACS Style

Benoit Guery; Julien Poissy; Loubna el Mansouf; Caroline Séjourné; Nicolas Ettahar; Xavier Lemaire; Fanny Vuotto; Anne Goffard; Sylvie Behillil; Vincent Enouf; Valérie Caro; Alexandra Mailles; Didier Che; Jean-Claude Manuguerra; Daniel Mathieu; Arnaud Fontanet; Sylvie van der Werf. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. The Lancet 2013, 381, 2265 -2272.

AMA Style

Benoit Guery, Julien Poissy, Loubna el Mansouf, Caroline Séjourné, Nicolas Ettahar, Xavier Lemaire, Fanny Vuotto, Anne Goffard, Sylvie Behillil, Vincent Enouf, Valérie Caro, Alexandra Mailles, Didier Che, Jean-Claude Manuguerra, Daniel Mathieu, Arnaud Fontanet, Sylvie van der Werf. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. The Lancet. 2013; 381 (9885):2265-2272.

Chicago/Turabian Style

Benoit Guery; Julien Poissy; Loubna el Mansouf; Caroline Séjourné; Nicolas Ettahar; Xavier Lemaire; Fanny Vuotto; Anne Goffard; Sylvie Behillil; Vincent Enouf; Valérie Caro; Alexandra Mailles; Didier Che; Jean-Claude Manuguerra; Daniel Mathieu; Arnaud Fontanet; Sylvie van der Werf. 2013. "Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission." The Lancet 381, no. 9885: 2265-2272.

Book chapter
Published: 27 February 2013 in Type 1 Diabetes
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ACS Style

Didier Hober; Famara Sane; Karena Riedweg; Ilham Moumna; Anne Goffard; Laura Choteau; Enagnon Kazali; Rachel Desaillou. Viruses and Type 1 Diabetes: Focus on the Enteroviruses. Type 1 Diabetes 2013, 1 .

AMA Style

Didier Hober, Famara Sane, Karena Riedweg, Ilham Moumna, Anne Goffard, Laura Choteau, Enagnon Kazali, Rachel Desaillou. Viruses and Type 1 Diabetes: Focus on the Enteroviruses. Type 1 Diabetes. 2013; ():1.

Chicago/Turabian Style

Didier Hober; Famara Sane; Karena Riedweg; Ilham Moumna; Anne Goffard; Laura Choteau; Enagnon Kazali; Rachel Desaillou. 2013. "Viruses and Type 1 Diabetes: Focus on the Enteroviruses." Type 1 Diabetes , no. : 1.

Journal article
Published: 01 January 2013 in Microbes and Infection
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Coxsackievirus B4 (CV-B4), in presence of antibodies and through a specific viral receptor CAR and Fcγ receptors II and III, can infect monocytes which results in interferon-α synthesis. The antibody-dependent enhancement of CV-B4 infection in the human monocytic-like THP-1 cell line has been investigated. The preincubation of CV-B4 with human plasma or human polyvalent immunoglobulins enhanced the infection of phorbol-myristate-acetate (PMA)-activated THP-1 cell cultures. CV-B4 replicated in these cells as demonstrated by the intracellular detection of infectious particles, viral protein VP1 (immunofluorescence), positive and negative viral RNA (RT-PCR). The viability of infected and control cell cultures was not different up to 20 days post-infection. Activated cell cultures inoculated with CV-B4 harbored intracellular RNA up to 14 days post-infection and produced IFNα that was detected by intracellular immunofluorescence staining as soon as 4 h post-infection with a maximum at 48 h post-infection and by RT-PCR all along the experiment. Together, these data demonstrate that PMA-activated THP-1 cells can be infected with CV-B4, can produce IFNα as a result of interactions between the virus, antibodies and specific receptors. This cellular model can be used to investigate further the mechanism and the result of the antibody-dependent enhancement of CV-B4 infection.

ACS Style

Anne Goffard; Enagnon Kazali Alidjinou; Famara Sane; L. Choteau; C. Bouquillon; D. Caloone; P.E. Lobert; D. Hober. Antibodies enhance the infection of phorbol-ester-differentiated human monocyte-like cells with coxsackievirus B4. Microbes and Infection 2013, 15, 18 -27.

AMA Style

Anne Goffard, Enagnon Kazali Alidjinou, Famara Sane, L. Choteau, C. Bouquillon, D. Caloone, P.E. Lobert, D. Hober. Antibodies enhance the infection of phorbol-ester-differentiated human monocyte-like cells with coxsackievirus B4. Microbes and Infection. 2013; 15 (1):18-27.

Chicago/Turabian Style

Anne Goffard; Enagnon Kazali Alidjinou; Famara Sane; L. Choteau; C. Bouquillon; D. Caloone; P.E. Lobert; D. Hober. 2013. "Antibodies enhance the infection of phorbol-ester-differentiated human monocyte-like cells with coxsackievirus B4." Microbes and Infection 15, no. 1: 18-27.

Review
Published: 02 March 2012 in Clinical & Experimental Immunology
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OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy. Type 1 diabetes results from an interaction between genetic and environmental factors. Coxsackieviruses B (CV‐B) are major environmental candidates, as suggested by epidemiological and experimental studies. The mechanisms leading to the disease involve interactions between the virus, host target tissue (pancreas) and the immune system. The infection of target cells with viruses can be prevented by antibodies. Conversely, the infection can be enhanced by antibodies. The antibody‐dependent enhancement (ADE) of infection has been described with various viruses, especially Picornaviruses. In mice infected with CV‐B3 this phenomenon resulted in an extended inflammatory reaction and myocarditis. In the human system non‐neutralizing antibodies can increase the infection of monocytes with CV‐B4 and stimulate the production of interferon (IFN)‐α by these cells in vitro. CV‐B4/immunoglobulin (Ig)G immune complexes interacted with a specific viral receptor [Coxsackievirus and adenovirus receptor (CAR)] and with IgG Fc fraction receptors (FcγRII and FcγRIII) at the surface of monocytes. The virus–antibody complexes are internalized (CAR) and receptors for the Fc of IgG (FcγRII and FcγRIII). Such antibodies have been detected in patients with type 1 diabetes and they could be responsible for the presence of enteroviral RNA and IFN‐α in peripheral blood mononuclear cells (PBMC) of these individuals. The target of enhancing antibodies has been identified as the VP4 protein, which allowed the detection of these antibodies by enzyme‐linked immunosorbent assay (ELISA). It cannot be excluded that antibodies enhancing the infection with CV‐B may play a role in the pathogenesis of type 1 diabetes, induced or aggravated by these viruses. They can cause a viral escape from the immune response and may participate in the spreading of viruses to β cells. Whether enhancing antibodies raised against VP4 can play a role in iterative homologous and/or heterologous CV‐B infections and in the persistence of viruses within the host deserves further study.

ACS Style

D. Hober; Famara Sane; Hela Jaïdane; K. Riedweg; Anne Goffard; Rachel Desailloud. Immunology in the clinic review series; focus on type 1 diabetes and viruses: role of antibodies enhancing the infection with Coxsackievirus-B in the pathogenesis of type 1 diabetes. Clinical & Experimental Immunology 2012, 168, 47 -51.

AMA Style

D. Hober, Famara Sane, Hela Jaïdane, K. Riedweg, Anne Goffard, Rachel Desailloud. Immunology in the clinic review series; focus on type 1 diabetes and viruses: role of antibodies enhancing the infection with Coxsackievirus-B in the pathogenesis of type 1 diabetes. Clinical & Experimental Immunology. 2012; 168 (1):47-51.

Chicago/Turabian Style

D. Hober; Famara Sane; Hela Jaïdane; K. Riedweg; Anne Goffard; Rachel Desailloud. 2012. "Immunology in the clinic review series; focus on type 1 diabetes and viruses: role of antibodies enhancing the infection with Coxsackievirus-B in the pathogenesis of type 1 diabetes." Clinical & Experimental Immunology 168, no. 1: 47-51.

Review
Published: 02 March 2012 in Clinical & Experimental Immunology
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Thymus dysfunction, especially immune suppression, is frequently associated with various virus infections. Whether viruses may disturb the thymus function and play a role in the pathogenesis of autoimmune diseases is an open issue. Enteroviruses, especially Coxsackievirus B4 (CV-B4), have been largely suggested as potential inducers or aggravating factors of type 1 diabetes (T1D) pathogenesis in genetically predisposed individuals. Several pathogenic mechanisms of enterovirus-induced T1D have been suggested. One of these mechanisms is the impairment of central self-tolerance due to viral infections. Coxsackievirus-B4 is able to infect murine thymus in vitro and in vivo and to infect human thymus in vitro. Thymic epithelial cells and thymocytes are targets of infection with this virus, and several abnormalities, especially disturbance of maturation/differentiation processes, were observed. Altogether, these data suggest that CV-B infection of thymus may be involved in the pathogenesis of T1D. Further investigations are needed to explore this hypothesis.

ACS Style

H. Jaïdane; F. Sané; R. Hiar; Anne Goffard; J. Gharbi; Vincent Geenen; D. Hober. Immunology in the clinic review series; focus on type 1 diabetes and viruses: enterovirus, thymus and type 1 diabetes pathogenesis. Clinical & Experimental Immunology 2012, 168, 39 -46.

AMA Style

H. Jaïdane, F. Sané, R. Hiar, Anne Goffard, J. Gharbi, Vincent Geenen, D. Hober. Immunology in the clinic review series; focus on type 1 diabetes and viruses: enterovirus, thymus and type 1 diabetes pathogenesis. Clinical & Experimental Immunology. 2012; 168 (1):39-46.

Chicago/Turabian Style

H. Jaïdane; F. Sané; R. Hiar; Anne Goffard; J. Gharbi; Vincent Geenen; D. Hober. 2012. "Immunology in the clinic review series; focus on type 1 diabetes and viruses: enterovirus, thymus and type 1 diabetes pathogenesis." Clinical & Experimental Immunology 168, no. 1: 39-46.

Journal article
Published: 01 August 2011 in Discovery medicine
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ACS Style

Anne Goffard; Famara Sané; Magali Soumillon; Didier Hober. Specificity of the coxsackievirus B4 VP4 capsid protein investigated in silico. Discovery medicine 2011, 12, 1 .

AMA Style

Anne Goffard, Famara Sané, Magali Soumillon, Didier Hober. Specificity of the coxsackievirus B4 VP4 capsid protein investigated in silico. Discovery medicine. 2011; 12 (63):1.

Chicago/Turabian Style

Anne Goffard; Famara Sané; Magali Soumillon; Didier Hober. 2011. "Specificity of the coxsackievirus B4 VP4 capsid protein investigated in silico." Discovery medicine 12, no. 63: 1.

Review
Published: 27 August 2010 in Reviews in Medical Virology
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Environmental factors, especially viruses, are involved in the initiation or the acceleration of type 1 diabetes (T1D) pathogenesis. Epidemiological data strongly suggest that enteroviruses, such as coxsackievirus B4 (CV‐B4), can be associated with T1D. It has been demonstrated that enterovirus infections were significantly more prevalent in at risk individuals, such as siblings of diabetic patients, when they developed anti‐β‐cell autoantibodies or T1D, and in recently diagnosed diabetic patients, compared with control subjects. The isolation of CV‐B4 from the pancreas of diabetic patients strengthened the hypothesis of a relationship between the virus and the disease. Studies performed in vitro and in vivo in animal models helped to discover mechanisms of the infection of pancreas and other tissues, potentially able to play a role in the pathogenesis of T1D. Interestingly, it cannot be excluded that enteroviruses behave as half‐devil half‐angel since experimental studies suggest that, in certain conditions, these agents would be able to protect individuals against the disease. All of the plausible mechanisms by which enterovirus may be related to T1D will be reviewed here. Copyright © 2010 John Wiley & Sons, Ltd.

ACS Style

Hela Jaïdane; Pierre Sauter; Famara Sane; Anne Goffard; Jawhar Gharbi; Didier Hober. Enteroviruses and type 1 diabetes: towards a better understanding of the relationship. Reviews in Medical Virology 2010, 20, 265 -280.

AMA Style

Hela Jaïdane, Pierre Sauter, Famara Sane, Anne Goffard, Jawhar Gharbi, Didier Hober. Enteroviruses and type 1 diabetes: towards a better understanding of the relationship. Reviews in Medical Virology. 2010; 20 (5):265-280.

Chicago/Turabian Style

Hela Jaïdane; Pierre Sauter; Famara Sane; Anne Goffard; Jawhar Gharbi; Didier Hober. 2010. "Enteroviruses and type 1 diabetes: towards a better understanding of the relationship." Reviews in Medical Virology 20, no. 5: 265-280.

Journal article
Published: 01 November 2009 in Journal of General Virology
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Co-infection and superinfection of hepatitis B virus (HBV) with hepatitis delta virus (HDV) leads to suppression of HBV replication both in patients and in animal and cellular models. The mechanisms behind this inhibition have not previously been explored fully. HBV replication is governed by four promoters and two enhancers, Enh1 and Enh2. Repression of these enhancers has been reported to be one of the main mechanisms of HBV inhibition. Moreover, in a previous study, it has been demonstrated that alpha interferon (IFN-α)-inducible MxA protein inhibits HBV replication. HDV encodes two proteins, p24 and p27. p27 was shown to activate several heterologous promoters, including HBV promoters. In an attempt to analyse the mechanisms of HBV inhibition by HDV, the question was raised whether HDV proteins could act directly by repressing HBV enhancers, and/or indirectly by activating the MxA gene. This issue was addressed in a co-transfection model in Huh-7 cells, using p24- or p27-expressing plasmids along with Enh1, Enh2, HBV and MxA promoter–luciferase constructs. Enh1 and Enh2 were strongly repressed, by 60 and 80 % and 40 and 60 %, by p24 and p27, respectively. In addition, p27 was responsible for threefold activation of the MxA promoter and potentiation of IFN-α on this promoter. MxA mRNA quantification and a virus yield reduction assay confirmed these results. In conclusion, this study shows that HDV proteins inhibit HBV replication by trans-repressing its enhancers and by trans-activating the IFN-α-inducible MxA gene.

ACS Style

Virginie Williams; Ségolène Brichler; Nadjia Radjef; Pierre Lebon; Anne Goffard; Didier Hober; Remi Fagard; Dina Kremsdorf; Paul Dény; Emmanuel Gordien. Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene. Journal of General Virology 2009, 90, 2759 -2767.

AMA Style

Virginie Williams, Ségolène Brichler, Nadjia Radjef, Pierre Lebon, Anne Goffard, Didier Hober, Remi Fagard, Dina Kremsdorf, Paul Dény, Emmanuel Gordien. Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene. Journal of General Virology. 2009; 90 (11):2759-2767.

Chicago/Turabian Style

Virginie Williams; Ségolène Brichler; Nadjia Radjef; Pierre Lebon; Anne Goffard; Didier Hober; Remi Fagard; Dina Kremsdorf; Paul Dény; Emmanuel Gordien. 2009. "Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene." Journal of General Virology 90, no. 11: 2759-2767.

English abstract
Published: 01 May 2009 in Pathologie Biologie
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Most of enterovirus infections are benign and the rate of mortality is low in countries with temperate climates. But since the late 1990s, Enterovirus 71 (EV-71) has become much more aggressive in Asian countries, with the outcome of a neurogenic pulmonary oedema syndrome and it is responsible for huge epidemics. The virological diagnosis rely upon viral isolation and identification by seroneutralisation, and upon the detection of specific IgM by ELISA and viral RNA by RT-PCR. There is no specific treatment to fight this virus, but innovative strategies, especially based on interfering RNA, are under investigation.

ACS Style

B. Kairis; P. Sauter; Anne Goffard; S. Fronval; F. Sané; D. Hober. Quand un entérovirus émerge. Pathologie Biologie 2009, 57, 258 -267.

AMA Style

B. Kairis, P. Sauter, Anne Goffard, S. Fronval, F. Sané, D. Hober. Quand un entérovirus émerge. Pathologie Biologie. 2009; 57 (3):258-267.

Chicago/Turabian Style

B. Kairis; P. Sauter; Anne Goffard; S. Fronval; F. Sané; D. Hober. 2009. "Quand un entérovirus émerge." Pathologie Biologie 57, no. 3: 258-267.

Journal article
Published: 19 January 2009 in Clinical Endocrinology
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Context Autoimmune thyroiditis is a very common disease. A genetic predisposition and environmental factors such as viruses are thought to contribute to the development of autoimmune thyroiditis. Enteroviruses, which are involved in other autoimmune diseases, are attractive candidates.

ACS Style

Rachel Desailloud; Anne Goffard; Cyril Page; Benoit Kairis; Stéphanie Fronval; Denis Chatelain; Vladimir Strunski; Alain Dubreuil; Didier Hober. Detection of enterovirus RNA in postoperative thyroid tissue specimens. Clinical Endocrinology 2009, 70, 331 -334.

AMA Style

Rachel Desailloud, Anne Goffard, Cyril Page, Benoit Kairis, Stéphanie Fronval, Denis Chatelain, Vladimir Strunski, Alain Dubreuil, Didier Hober. Detection of enterovirus RNA in postoperative thyroid tissue specimens. Clinical Endocrinology. 2009; 70 (2):331-334.

Chicago/Turabian Style

Rachel Desailloud; Anne Goffard; Cyril Page; Benoit Kairis; Stéphanie Fronval; Denis Chatelain; Vladimir Strunski; Alain Dubreuil; Didier Hober. 2009. "Detection of enterovirus RNA in postoperative thyroid tissue specimens." Clinical Endocrinology 70, no. 2: 331-334.