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I obtained my PhD in Molecular Virology at the Faculty of Medicine in Geneva. After postdoctoral trainings in human genetics and bacteriology, I became group leader at the University Hospitals of Geneva in 2005 and Professor at the Faculty of Medicine of the University of Geneva in 2014. The aims of my research are to study the pathogenesis of respiratory and neurotropic viruses (with special emphasis on rhinoviruses and enteroviruses) using relevant 3D tissues culture models and clinical viral strains; to determine the genetic determinants of specific features such as virulence, dissemination and neurotropism; and finally to develop efficient and broad-spectrum antiviral therapies.
Enteroviruses (EVs) from the D species are the causative agents of a diverse range of infectious diseases in spite of comprising only five known members. This small clade has a diverse host range and tissue tropism. It contains types infecting non-human primates and/or humans, and for the latter, they preferentially infect the eye, respiratory tract, gastrointestinal tract, and nervous system. Although several Enterovirus D members, in particular EV-D68, have been associated with neurological complications, including acute myelitis, there is currently no effective treatment or vaccine against any of them. This review highlights the peculiarities of this viral species, focusing on genome organization, functional elements, receptor usage, and pathogenesis.
Ines Cordeiro Filipe; Mariana Soares Guedes; Evgeny M. Zdobnov; Caroline Tapparel. Enterovirus D: A Small but Versatile Species. Microorganisms 2021, 9, 1758 .
AMA StyleInes Cordeiro Filipe, Mariana Soares Guedes, Evgeny M. Zdobnov, Caroline Tapparel. Enterovirus D: A Small but Versatile Species. Microorganisms. 2021; 9 (8):1758.
Chicago/Turabian StyleInes Cordeiro Filipe; Mariana Soares Guedes; Evgeny M. Zdobnov; Caroline Tapparel. 2021. "Enterovirus D: A Small but Versatile Species." Microorganisms 9, no. 8: 1758.
Methylene blue is an FDA (Food and Drug Administration) and EMA (European Medicines Agency) approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. In this study, we first evaluated the virucidal activity of methylene blue against influenza virus H1N1 upon different incubation times and in the presence or absence of light activation, and then against SARS-CoV-2. We further assessed the therapeutic activity of methylene blue by administering it to cells previously infected with SARS-CoV-2. Finally, we examined the effect of co-administration of the drug together with immune serum. Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against influenza virus H1N1 and SARS-CoV-2 at low micromolar concentrations and in the absence of UV-activation. We also confirm that MB antiviral activity is based on several mechanisms of action as the extent of genomic RNA degradation is higher in presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive and/or therapeutic efficacy against both influenza virus H1N1 and SARS-CoV-2 infections.
Valeria Cagno; Chiara Medaglia; Andreas Cerny; Thomas Cerny; Arnaud Charles-Antoine Zwygart; Erich Cerny; Caroline Tapparel. Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro. Scientific Reports 2021, 11, 1 -8.
AMA StyleValeria Cagno, Chiara Medaglia, Andreas Cerny, Thomas Cerny, Arnaud Charles-Antoine Zwygart, Erich Cerny, Caroline Tapparel. Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro. Scientific Reports. 2021; 11 (1):1-8.
Chicago/Turabian StyleValeria Cagno; Chiara Medaglia; Andreas Cerny; Thomas Cerny; Arnaud Charles-Antoine Zwygart; Erich Cerny; Caroline Tapparel. 2021. "Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro." Scientific Reports 11, no. 1: 1-8.
Influenza viruses are a leading cause of morbidity and mortality worldwide. These air-borne pathogens are able to cross the species barrier, leading to regular seasonal epidemics and sporadic pandemics. Influenza viruses also possess a high genetic variability, which allows for the acquisition of resistance mutations to antivirals. Combination therapies with two or more drugs targeting different mechanisms of viral replication have been considered an advantageous option to not only enhance the effectiveness of the individual treatments, but also reduce the likelihood of resistance emergence. Using an in vitro infection model, we assessed the barrier to viral resistance of a combination therapy with the neuraminidase inhibitor oseltamivir and human interferon lambda against the pandemic H1N1 A/Netherlands/602/2009 (H1N1pdm09) virus. We serially passaged the virus in a cell line derived from human bronchial epithelial cells in the presence or absence of increasing concentrations of oseltamivir alone or oseltamivir plus interferon lambda. While the treatment with oseltamivir alone quickly induced the emergence of antiviral resistance through a single mutation in the neuraminidase gene, the co-administration of interferon lambda delayed the emergence of drug-resistant influenza virus variants. Our results suggest a possible clinical application of interferon lambda in combination with oseltamivir to treat influenza.
Chiara Medaglia; Arnaud Zwygart; Paulo Silva; Samuel Constant; Song Huang; Francesco Stellacci; Caroline Tapparel. Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir. Microorganisms 2021, 9, 1196 .
AMA StyleChiara Medaglia, Arnaud Zwygart, Paulo Silva, Samuel Constant, Song Huang, Francesco Stellacci, Caroline Tapparel. Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir. Microorganisms. 2021; 9 (6):1196.
Chicago/Turabian StyleChiara Medaglia; Arnaud Zwygart; Paulo Silva; Samuel Constant; Song Huang; Francesco Stellacci; Caroline Tapparel. 2021. "Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir." Microorganisms 9, no. 6: 1196.
Methylene blue is an FDA (food and drug administration) and EMA (european medicines agency) approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. In this study, we first evaluated the virucidal activity of methylene blue against Influenza Virus H1N1 upon different incubation times and in the presence or absence of light activation, and then against SARS-CoV-2. We further assessed the therapeutic activity of methylene blue by administering it to cells previously infected with SARS-CoV-2. Finally, we examined the effect of co-administration of the drug together with immune serum. Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against Influenza Virus H1N1 and SARS-CoV-2 at low micromolar concentrations and in the absence of UV activation. We also confirm that MB antiviral activity is based on several mechanisms of action as the degradation of genomic RNA is only observed in the presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive or therapeutic efficacy against both Influenza Virus H1N1 and SARS-CoV-2 infections.
Valeria Cagno1; Chiara Medaglia; Andreas Cerny; Thomas Cerny; Arnaud Zwygart; Erich Cerny; Caroline Tapparel. Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro. 2021, 1 .
AMA StyleValeria Cagno1, Chiara Medaglia, Andreas Cerny, Thomas Cerny, Arnaud Zwygart, Erich Cerny, Caroline Tapparel. Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro. . 2021; ():1.
Chicago/Turabian StyleValeria Cagno1; Chiara Medaglia; Andreas Cerny; Thomas Cerny; Arnaud Zwygart; Erich Cerny; Caroline Tapparel. 2021. "Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro." , no. : 1.
Respiratory viral infections constitute a global public health concern. Among prevalent respiratory viruses, two pneumoviruses can be life-threatening in high-risk populations. In young children, they constitute the first cause of hospitalization due to severe lower respiratory tract diseases. A better understanding of their pathogenesis is still needed as there are no approved efficient anti-viral nor vaccine against pneumoviruses. We studied Respiratory Syncytial virus (RSV) and human Metapneumovirus (HMPV) in single and dual infections in three-dimensional cultures, a highly relevant model to study viral respiratory infections of the airway epithelium. Our investigation showed that HMPV is less pathogenic than RSV in this model. Compared to RSV, HMPV replicated less efficiently, induced a lower immune response, did not block cilia beating, and was more sensitive to IFNs. In dual infections, RSV-infected epithelia were less permissive to HMPV. By neutralizing IFNs in co-infection assays, we partially prevented HMPV inhibition by RSV and significantly increased the number of co-infected cells in the tissue. This suggests that interference in dual infection would be at least partly mediated by the host immune response. In summary, this work provides new insight regarding virus-host and virus-virus interactions of pneumoviruses in the airway epithelium. This could be helpful for the proper handling of at-risk patients.
Johan Geiser; Guy Boivin; Song Huang; Samuel Constant; Laurent Kaiser; Caroline Tapparel; Manel Essaidi-Laziosi. RSV and HMPV Infections in 3D Tissue Cultures: Mechanisms Involved in Virus-Host and Virus-Virus Interactions. Viruses 2021, 13, 139 .
AMA StyleJohan Geiser, Guy Boivin, Song Huang, Samuel Constant, Laurent Kaiser, Caroline Tapparel, Manel Essaidi-Laziosi. RSV and HMPV Infections in 3D Tissue Cultures: Mechanisms Involved in Virus-Host and Virus-Virus Interactions. Viruses. 2021; 13 (1):139.
Chicago/Turabian StyleJohan Geiser; Guy Boivin; Song Huang; Samuel Constant; Laurent Kaiser; Caroline Tapparel; Manel Essaidi-Laziosi. 2021. "RSV and HMPV Infections in 3D Tissue Cultures: Mechanisms Involved in Virus-Host and Virus-Virus Interactions." Viruses 13, no. 1: 139.
Poliomyelitis is caused by poliovirus (PV), a positive strand non-enveloped virus. Since its discovery in the 1950s, several cell culture and molecular methods have been developed to detect and characterize the various strains of PV. Here, we provide an accurate and standardized protocol to differentiate human embryonic stem cells (hESCs) toward engineered neural tissue enriched with motor neurons (MN ENTs). These MN ENTs expressed markers of motor neuron CHAT and Hb-9 as revealed by immunofluorescence staining and quantitative RT-PCR. Interestingly, our results suggest that motor neurons are responsible for the permissiveness of poliovirus within the MN ENTs. Moreover, our study revealed the molecular events occurring upon PV-3 infection in the MN ENTs and highlighted the modulation of a set of genes involved in EGR-EP300 complex. Collectively, we report the development of a reliable in vitro model to investigate the pathophysiology of PV infection, allowing to both design and assess novel therapeutic approaches against PV infection.
Érika Cosset; Youssef Hibaoui; Sten Ilmjärv; Pierre-Yves Dietrich; Caroline Tapparel; Karl-Heinz Krause. Modeling Poliovirus Infection Using Human Engineered Neural Tissue Enriched With Motor Neuron Derived From Embryonic Stem Cells. Frontiers in Cell and Developmental Biology 2021, 8, 1 .
AMA StyleÉrika Cosset, Youssef Hibaoui, Sten Ilmjärv, Pierre-Yves Dietrich, Caroline Tapparel, Karl-Heinz Krause. Modeling Poliovirus Infection Using Human Engineered Neural Tissue Enriched With Motor Neuron Derived From Embryonic Stem Cells. Frontiers in Cell and Developmental Biology. 2021; 8 ():1.
Chicago/Turabian StyleÉrika Cosset; Youssef Hibaoui; Sten Ilmjärv; Pierre-Yves Dietrich; Caroline Tapparel; Karl-Heinz Krause. 2021. "Modeling Poliovirus Infection Using Human Engineered Neural Tissue Enriched With Motor Neuron Derived From Embryonic Stem Cells." Frontiers in Cell and Developmental Biology 8, no. : 1.
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) depends on angiotensin converting enzyme 2 (ACE2) for cellular entry, but it might also rely on attachment receptors such as heparan sulfates. Several groups have recently demonstrated an affinity of the SARS-CoV2 spike protein for heparan sulfates and a reduced binding to cells in the presence of heparin or heparinase treatment. Here, we investigated the inhibitory activity of several sulfated and sulfonated molecules, which prevent interaction with heparan sulfates, against vesicular stomatitis virus (VSV)-pseudotyped-SARS-CoV-2 and the authentic SARS-CoV-2. Sulfonated cyclodextrins and nanoparticles that have recently shown broad-spectrum non-toxic virucidal activity against many heparan sulfates binding viruses showed inhibitory activity in the micromolar and nanomolar ranges, respectively. In stark contrast with the mechanisms that these compounds present for these other viruses, the inhibition against SARS-CoV-2 was found to be simply reversible.
Matteo Gasbarri; Philip V’Kovski; Giulia Torriani; Volker Thiel; Francesco Stellacci; Caroline Tapparel; Valeria Cagno. SARS-CoV-2 Inhibition by Sulfonated Compounds. Microorganisms 2020, 8, 1894 .
AMA StyleMatteo Gasbarri, Philip V’Kovski, Giulia Torriani, Volker Thiel, Francesco Stellacci, Caroline Tapparel, Valeria Cagno. SARS-CoV-2 Inhibition by Sulfonated Compounds. Microorganisms. 2020; 8 (12):1894.
Chicago/Turabian StyleMatteo Gasbarri; Philip V’Kovski; Giulia Torriani; Volker Thiel; Francesco Stellacci; Caroline Tapparel; Valeria Cagno. 2020. "SARS-CoV-2 Inhibition by Sulfonated Compounds." Microorganisms 8, no. 12: 1894.
Animal models and cell lines are invaluable for virology research and host–pathogen interaction studies. However, it is increasingly evident that these models are not sufficient to fully understand human viral diseases. With the advent of three-dimensional organotypic cultures, it is now possible to study viral infections in the human context. This perspective explores the potential of these organotypic cultures, also known as organoids, for virology research, antiviral testing, and shaping the virology landscape.
Adithya Sridhar; Salvatore Simmini; Carla M. S. Ribeiro; Caroline Tapparel; Melvin M. Evers; Dasja Pajkrt; Katja Wolthers. A Perspective on Organoids for Virology Research. Viruses 2020, 12, 1341 .
AMA StyleAdithya Sridhar, Salvatore Simmini, Carla M. S. Ribeiro, Caroline Tapparel, Melvin M. Evers, Dasja Pajkrt, Katja Wolthers. A Perspective on Organoids for Virology Research. Viruses. 2020; 12 (11):1341.
Chicago/Turabian StyleAdithya Sridhar; Salvatore Simmini; Carla M. S. Ribeiro; Caroline Tapparel; Melvin M. Evers; Dasja Pajkrt; Katja Wolthers. 2020. "A Perspective on Organoids for Virology Research." Viruses 12, no. 11: 1341.
Viral infections are among the main causes of death worldwide, and we lack antivirals for the majority of viruses. Heparin-like sulfated or sulfonated compounds have been known for decades for their ability to prevent infection by heparan sulfate proteoglycan (HSPG)-dependent viruses but only in a reversible way. We have previously shown that gold nanoparticles and β-cyclodextrins coated with mercapto-undecane sulfonic acid (MUS) inhibit HSPG-dependent viruses irreversibly while retaining the low-toxicity profile of most heparin-like compounds.
Valeria Cagno; Matteo Gasbarri; Chiara Medaglia; Diana Gomes; Sophie Clement; Francesco Stellacci; Caroline Tapparel. Sulfonated Nanomaterials with Broad-Spectrum Antiviral Activity Extending beyond Heparan Sulfate-Dependent Viruses. Antimicrobial Agents and Chemotherapy 2020, 64, 1 .
AMA StyleValeria Cagno, Matteo Gasbarri, Chiara Medaglia, Diana Gomes, Sophie Clement, Francesco Stellacci, Caroline Tapparel. Sulfonated Nanomaterials with Broad-Spectrum Antiviral Activity Extending beyond Heparan Sulfate-Dependent Viruses. Antimicrobial Agents and Chemotherapy. 2020; 64 (12):1.
Chicago/Turabian StyleValeria Cagno; Matteo Gasbarri; Chiara Medaglia; Diana Gomes; Sophie Clement; Francesco Stellacci; Caroline Tapparel. 2020. "Sulfonated Nanomaterials with Broad-Spectrum Antiviral Activity Extending beyond Heparan Sulfate-Dependent Viruses." Antimicrobial Agents and Chemotherapy 64, no. 12: 1.
Methylene blue is an FDA and EMA approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. Here we show the virucidal activity of methylene blue at low micromolar concentrations and in the absence of UV activation against SARS-CoV2.
Valeria Cagno; Chiara Medaglia; Andreas Cerny; Thomas Cerny; Caroline Tapparel; Erich Cerny. Methylene Blue has a potent antiviral activity against SARS-CoV-2 in the absence of UV-activation in vitro. 2020, 1 .
AMA StyleValeria Cagno, Chiara Medaglia, Andreas Cerny, Thomas Cerny, Caroline Tapparel, Erich Cerny. Methylene Blue has a potent antiviral activity against SARS-CoV-2 in the absence of UV-activation in vitro. . 2020; ():1.
Chicago/Turabian StyleValeria Cagno; Chiara Medaglia; Andreas Cerny; Thomas Cerny; Caroline Tapparel; Erich Cerny. 2020. "Methylene Blue has a potent antiviral activity against SARS-CoV-2 in the absence of UV-activation in vitro." , no. : 1.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Manel Essaidi-Laziosi; Johan Geiser; Song Huang; Samuel Constant; Laurent Kaiser; Caroline Tapparel. Author Correction: Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia. Scientific Reports 2020, 10, 1 -1.
AMA StyleManel Essaidi-Laziosi, Johan Geiser, Song Huang, Samuel Constant, Laurent Kaiser, Caroline Tapparel. Author Correction: Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia. Scientific Reports. 2020; 10 (1):1-1.
Chicago/Turabian StyleManel Essaidi-Laziosi; Johan Geiser; Song Huang; Samuel Constant; Laurent Kaiser; Caroline Tapparel. 2020. "Author Correction: Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia." Scientific Reports 10, no. 1: 1-1.
Many respiratory viruses cocirculate in the population and multiple infections are commonly reported. The clinical impact of coinfection is unclear and may vary depending on the viral couples involved. Using three-dimensional reconstituted human airway epithelia and clinical viral strains, we investigated the interaction between influenza virus (Flu), respiratory syncytial virus (RSV) and rhinovirus (RV). We showed that Flu and RSV interfere with RV replication, whereas RV does not interfere with either of these viruses. We then experimentally demonstrated that, when present, the interference is not related to a block of viral entry but rather to type I and type III interferon (IFN), the front-line antiviral defense of the respiratory mucosa. Consistent with this observation, we highlighted the differential sensitivity of each virus to IFNs, with RV being the only virus significantly inhibited by IFN-λ and the most sensitive to IFN-α. Finally, as type III IFN is of therapeutic interest due to its low proinflammatory profile, we also assessed and confirmed an inhibitory effect of IFN-λ in the context of persistent RV infections. The present work provides mechanistic clues concerning innate immunity involvement during respiratory virus interactions and confirms that IFN-λ is a promising candidate in the treatment of RV infections.
Manel Essaidi-Laziosi; Johan Geiser; Song Huang; Samuel Constant; Laurent Kaiser; Caroline Tapparel. Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia. Scientific Reports 2020, 10, 1 -9.
AMA StyleManel Essaidi-Laziosi, Johan Geiser, Song Huang, Samuel Constant, Laurent Kaiser, Caroline Tapparel. Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia. Scientific Reports. 2020; 10 (1):1-9.
Chicago/Turabian StyleManel Essaidi-Laziosi; Johan Geiser; Song Huang; Samuel Constant; Laurent Kaiser; Caroline Tapparel. 2020. "Interferon-Dependent and Respiratory Virus-Specific Interference in Dual Infections of Airway Epithelia." Scientific Reports 10, no. 1: 1-9.
Influenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is very high. It is very important to develop broad-spectrum influenza antivirals to be ready for any possible vaccine shortcomings. Anti-influenza drugs are available but they are far from ideal. Arguably, an ideal antiviral should target conserved viral domains and be virucidal, i.e. irreversibly inhibit viral infectivity. Here, we describe a new class of broad-spectrum anti-influenza macromolecules that meets these criteria and displays exceedingly low toxicity. These compounds are based on a cyclodextrin core modified on its primary face with long hydrophobic linkers terminated in 6’sialyl-N-acetyllactosamine (6’SLN) or 3’SLN. SLN enables nanomolar inhibition of the viruses while the hydrophobic linkers confer irreversibility to the inhibition. The combination of these two properties allows for efficacy in vitro against several human or avian influenza strains, as well as against a 2009 pandemic influenza strain ex vivo. Importantly, we show that, in mice, the compounds provide therapeutic efficacy when administered 24h post-infection allowing 90% survival as opposed to no survival for the placebo and oseltamivir..
Ozgun Kocabiyik; Valeria Cagno; Paulo Jacob Silva; Yong Zhu; Laura Sedano; Yoshita Bhide; Joelle Mettier; Chiara Medaglia; Bruno Da Costa; Samuel Constant; Song Huang; Laurent Kaiser; Wouter L. J. Hinrichs; Anke Huckeriede; Ronan Le Goffic; Caroline Tapparel; Francesco Stellacci. Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo. 2020, 1 .
AMA StyleOzgun Kocabiyik, Valeria Cagno, Paulo Jacob Silva, Yong Zhu, Laura Sedano, Yoshita Bhide, Joelle Mettier, Chiara Medaglia, Bruno Da Costa, Samuel Constant, Song Huang, Laurent Kaiser, Wouter L. J. Hinrichs, Anke Huckeriede, Ronan Le Goffic, Caroline Tapparel, Francesco Stellacci. Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo. . 2020; ():1.
Chicago/Turabian StyleOzgun Kocabiyik; Valeria Cagno; Paulo Jacob Silva; Yong Zhu; Laura Sedano; Yoshita Bhide; Joelle Mettier; Chiara Medaglia; Bruno Da Costa; Samuel Constant; Song Huang; Laurent Kaiser; Wouter L. J. Hinrichs; Anke Huckeriede; Ronan Le Goffic; Caroline Tapparel; Francesco Stellacci. 2020. "Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo." , no. : 1.
Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.
Samuel T. Jones; Valeria Cagno; Matej Janeček; Daniel Ortiz; Natalia Gasilova; Jocelyne Piret; Matteo Gasbarri; David A. Constant; Yanxiao Han; Lela Vuković; Petr Král; Laurent Kaiser; Song Huang; Samuel Constant; Karla Kirkegaard; Guy Boivin; Francesco Stellacci; Caroline Tapparel. Modified cyclodextrins as broad-spectrum antivirals. Science Advances 2020, 6, eaax9318 .
AMA StyleSamuel T. Jones, Valeria Cagno, Matej Janeček, Daniel Ortiz, Natalia Gasilova, Jocelyne Piret, Matteo Gasbarri, David A. Constant, Yanxiao Han, Lela Vuković, Petr Král, Laurent Kaiser, Song Huang, Samuel Constant, Karla Kirkegaard, Guy Boivin, Francesco Stellacci, Caroline Tapparel. Modified cyclodextrins as broad-spectrum antivirals. Science Advances. 2020; 6 (5):eaax9318.
Chicago/Turabian StyleSamuel T. Jones; Valeria Cagno; Matej Janeček; Daniel Ortiz; Natalia Gasilova; Jocelyne Piret; Matteo Gasbarri; David A. Constant; Yanxiao Han; Lela Vuković; Petr Král; Laurent Kaiser; Song Huang; Samuel Constant; Karla Kirkegaard; Guy Boivin; Francesco Stellacci; Caroline Tapparel. 2020. "Modified cyclodextrins as broad-spectrum antivirals." Science Advances 6, no. 5: eaax9318.
Heparan sulfate proteoglycans (HSPG) are composed of unbranched, negatively charged heparan sulfate (HS) polysaccharides attached to a variety of cell surface or extracellular matrix proteins. Widely expressed, they mediate many biological activities, including angiogenesis, blood coagulation, developmental processes, and cell homeostasis. HSPG are highly sulfated and broadly used by a range of pathogens, especially viruses, to attach to the cell surface.
Valeria Cagno; Eirini D. Tseligka; Samuel T. Jones; Caroline Tapparel. Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias? Viruses 2019, 11, 596 .
AMA StyleValeria Cagno, Eirini D. Tseligka, Samuel T. Jones, Caroline Tapparel. Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias? Viruses. 2019; 11 (7):596.
Chicago/Turabian StyleValeria Cagno; Eirini D. Tseligka; Samuel T. Jones; Caroline Tapparel. 2019. "Heparan Sulfate Proteoglycans and Viral Attachment: True Receptors or Adaptation Bias?" Viruses 11, no. 7: 596.
Zika virus (ZIKV) is mostly mosquito borne but can also be transmitted by the sexual route, and persist in semen for prolonged time. Moreover, viral RNA has been detected in breastmilk, saliva, lacrimal fluids and urines, suggesting other possible transmission routes. The aim of our research is to better define ZIKV tropism. We investigated the tropism of ZIKV Asian and African strains using human-derived neural, vaginal, intestinal and respiratory tissues. ZIKV Asian and African strains were able to grow in all tissues tested, although with different efficiency (7.3 log RNA copies released apically in vaginal tissues versus 9.8 log RNA copies released in intestinal tissues), without the need of major adaptation. Our results underline that ZIKV tropism may be broader than expected in humans and stresses the need to better explore all possible viral shedding sites and transmission routes.
Valeria Cagno; Eirini D. Tseligka; Quentin Bettex; Song Huang; Samuel Constant; Caroline Tapparel. Growth of Zika virus in human reconstituted respiratory, intestinal, vaginal and neural tissues. Clinical Microbiology and Infection 2019, 25, 1042.e1 -1042.e4.
AMA StyleValeria Cagno, Eirini D. Tseligka, Quentin Bettex, Song Huang, Samuel Constant, Caroline Tapparel. Growth of Zika virus in human reconstituted respiratory, intestinal, vaginal and neural tissues. Clinical Microbiology and Infection. 2019; 25 (8):1042.e1-1042.e4.
Chicago/Turabian StyleValeria Cagno; Eirini D. Tseligka; Quentin Bettex; Song Huang; Samuel Constant; Caroline Tapparel. 2019. "Growth of Zika virus in human reconstituted respiratory, intestinal, vaginal and neural tissues." Clinical Microbiology and Infection 25, no. 8: 1042.e1-1042.e4.
Enterovirus 71 (EV71) causes hand, foot and mouth disease, a mild and self-limited illness that is sometimes associated with severe neurological complications. EV71 neurotropic determinants remain ill-defined to date. We previously identified a mutation in the VP1 capsid protein (L97R) that was acquired over the course of a disseminated infection in an immunocompromised host. The mutation was absent in the respiratory tract but was present in the gut (as a mixed population) and in blood and cerebrospinal fluid (as a dominant species). In this study, we demonstrated that this mutation does not alter the dependence of EV71 on the human scavenger receptor class B2 (SCARB2), while it enables the virus to bind to the heparan sulfate (HS) attachment receptor and modifies viral tropism in cell lines and in respiratory, intestinal and neural tissues. Variants with VP197L or VP197R were able to replicate to high levels in intestinal and neural tissues and, to a lesser extent, in respiratory tissues, but their preferred entry site (from the luminal or basal tissue side) differed in respiratory and intestinal tissues and correlated with HS expression levels. These data account for the viral populations sequenced from the patient’s respiratory and intestinal samples and suggest that improved dissemination, resulting from an acquired ability to bind HS, rather than specific neurotropism determinants, enabled the virus to reach and infect the central nervous system. Finally, we showed that iota-carrageenan, a highly sulfated polysaccharide, efficiently blocks the replication of HS-dependent variants in cells and 2D neural cultures. Overall, the results of this study emphasize the importance of HS binding in EV71 pathogenesis and open new avenues for the development of antiviral molecules that may prevent this virus’s dissemination. Enterovirus 71 (EV71) has been the cause of major hand-foot-and-mouth disease outbreaks, particularly in the Asia-Pacific region. However, the recent emergence of severe neurological cases associated with EV71 infection in Europe and the lack of an efficient vaccine or antiviral agent to fight EV71 infections highlight two critical needs: (A) the identification of ill-defined viral factors that contribute to viral dissemination and pathogenesis in humans and (B) the development of effective antiviral strategies. Herein, based on clinical observation in an immunocompromised host, we have demonstrated that heparan sulfate attachment receptor played a critical role in EV71 virulence and that “in host” EV71 adaptation to a heparan sulfate-dependent virus was likely responsible for its dissemination. To our knowledge, this is the first study highlighting the key determinants of EV71 dissemination based on a clinical case and proposing a new therapeutic approach against EV71 neurological diseases.
Eirini D. Tseligka; Komla Sobo; Luc Stoppini; Valeria Cagno; Fabien Abdul; Isabelle Piuz; Pascal Meylan; Song Huang; Samuel Constant; Caroline Tapparel. A VP1 mutation acquired during an enterovirus 71 disseminated infection confers heparan sulfate binding ability and modulates ex vivo tropism. PLOS Pathogens 2018, 14, e1007190 .
AMA StyleEirini D. Tseligka, Komla Sobo, Luc Stoppini, Valeria Cagno, Fabien Abdul, Isabelle Piuz, Pascal Meylan, Song Huang, Samuel Constant, Caroline Tapparel. A VP1 mutation acquired during an enterovirus 71 disseminated infection confers heparan sulfate binding ability and modulates ex vivo tropism. PLOS Pathogens. 2018; 14 (8):e1007190.
Chicago/Turabian StyleEirini D. Tseligka; Komla Sobo; Luc Stoppini; Valeria Cagno; Fabien Abdul; Isabelle Piuz; Pascal Meylan; Song Huang; Samuel Constant; Caroline Tapparel. 2018. "A VP1 mutation acquired during an enterovirus 71 disseminated infection confers heparan sulfate binding ability and modulates ex vivo tropism." PLOS Pathogens 14, no. 8: e1007190.
Despite their genetic similarities, enteric and respiratory enteroviruses (EVs) have highly heterogeneous biophysical properties and cause a vast diversity of human pathologies. In vitro differences include acid sensitivity, optimal growth temperature and tissue tropism, which reflect a preferential in vivo replication in the respiratory or gastrointestinal tract and are thus key determinants of EV virulence. To investigate the underlying cause of these differences, we generated chimeras at the capsid-level between EV-D68 (a respiratory EV) and EV-D94 (an enteric EV). Although some chimeras were nonfunctional, EV-D94 with both the capsid and 2A protease or the capsid only of EV-D68 were both viable. Using this latter construct, we performed several functional assays, which indicated that capsid proteins determine acid sensitivity and tropism in cell lines and in respiratory, intestinal and neural tissues. Additionally, capsid genes were shown to also participate in determining the optimal growth temperature, since EV-D94 temperature adaptation relied on single mutations in VP1, while constructs with EV-D68 capsid could not adapt to higher temperatures. Finally, we demonstrate that EV-D68 maintains residual binding-capacity after acid-treatment despite a loss of infectivity. In contrast, non-structural rather than capsid proteins modulate the innate immune response in tissues. These unique biophysical insights expose another layer in the phenotypic diversity of one of world’s most prevalent pathogens and could aid target selection for vaccine or antiviral development. Enteroviruses (EV) are one of the most frequent human pathogens worldwide, causing a broad spectrum of diseases, ranging from the common cold to fatal flaccid paralysis. Surprisingly, this vast phenotypic diversity is not reflected at the genetic level, where despite intensive research, the factors contributing to these variations remain poorly understood. By generating novel chimeric viruses derived from a respiratory (EV-D68) and an enteric (EV-D94) EV, we highlight the crucial role of capsid proteins in acid sensitivity, in vitro tropism and optimal growth temperature. We also show that while capsid proteins are central to the biophysical viability of EV, they elicit only minor effects on the innate immune response. This work identifies key players in the pathogenesis of these highly prevalent viruses, which not only improves our understanding of their biology, but may also better guide the selection of new targets for vaccine and antiviral innovations.
Léna Royston; Manel Essaidi-Laziosi; Francisco J. Pérez-Rodríguez; Isabelle Piuz; Johan Geiser; Karl-Heinz Krause; Song Huang; Samuel Constant; Laurent Kaiser; Dominique Garcin; Caroline Tapparel. Viral chimeras decrypt the role of enterovirus capsid proteins in viral tropism, acid sensitivity and optimal growth temperature. PLOS Pathogens 2018, 14, e1006962 .
AMA StyleLéna Royston, Manel Essaidi-Laziosi, Francisco J. Pérez-Rodríguez, Isabelle Piuz, Johan Geiser, Karl-Heinz Krause, Song Huang, Samuel Constant, Laurent Kaiser, Dominique Garcin, Caroline Tapparel. Viral chimeras decrypt the role of enterovirus capsid proteins in viral tropism, acid sensitivity and optimal growth temperature. PLOS Pathogens. 2018; 14 (4):e1006962.
Chicago/Turabian StyleLéna Royston; Manel Essaidi-Laziosi; Francisco J. Pérez-Rodríguez; Isabelle Piuz; Johan Geiser; Karl-Heinz Krause; Song Huang; Samuel Constant; Laurent Kaiser; Dominique Garcin; Caroline Tapparel. 2018. "Viral chimeras decrypt the role of enterovirus capsid proteins in viral tropism, acid sensitivity and optimal growth temperature." PLOS Pathogens 14, no. 4: e1006962.
Background The leading cause of acute illnesses, respiratory viruses, typically cause self-limited diseases, although severe complications can occur in fragile patients. Rhinoviruses (RVs), respiratory enteroviruses (EVs), influenza virus, respiratory syncytial viruses (RSVs), and coronaviruses are highly prevalent respiratory pathogens, but because of the lack of reliable animal models, their differential pathogenesis remains poorly characterized. Objective We sought to compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Methods Tissues were infected with RV-A55, RV-A49, RV-B48, RV-C8, and RV-C15; respiratory EV-D68; influenza virus H3N2; RSV-B; and human coronavirus (HCoV)–OC43. Replication kinetics, cell tropism, effect on tissue integrity, and cytokine secretion were compared. Viral adaptation and tissue response were assessed through RNA sequencing. Results RVs, RSV-B, and HCoV-OC43 infected ciliated cells and caused no major cell death, whereas H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses, except RV-B48 and HCoV-OC43, altered cilia beating and mucociliary clearance. H3N2 was the strongest cytokine inducer, and HCoV-OC43 was the weakest. Persistent infection was observed in all cases. RNA sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4 days after infection. No majority mutations emerged in the viral population. Conclusion Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory tract infections in immunocompromised hosts.
Manel Essaidi-Laziosi; Francisco Brito; Sacha Benaoudia; Léna Royston; Valeria Cagno; Mélanie Fernandes-Rocha; Isabelle Piuz; Evgeny Zdobnov; Song Huang; Samuel Constant; Marc-Olivier Boldi; Laurent Kaiser; Caroline Tapparel. Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures. Journal of Allergy and Clinical Immunology 2017, 141, 2074 -2084.
AMA StyleManel Essaidi-Laziosi, Francisco Brito, Sacha Benaoudia, Léna Royston, Valeria Cagno, Mélanie Fernandes-Rocha, Isabelle Piuz, Evgeny Zdobnov, Song Huang, Samuel Constant, Marc-Olivier Boldi, Laurent Kaiser, Caroline Tapparel. Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures. Journal of Allergy and Clinical Immunology. 2017; 141 (6):2074-2084.
Chicago/Turabian StyleManel Essaidi-Laziosi; Francisco Brito; Sacha Benaoudia; Léna Royston; Valeria Cagno; Mélanie Fernandes-Rocha; Isabelle Piuz; Evgeny Zdobnov; Song Huang; Samuel Constant; Marc-Olivier Boldi; Laurent Kaiser; Caroline Tapparel. 2017. "Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures." Journal of Allergy and Clinical Immunology 141, no. 6: 2074-2084.