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Hulda R. Jonsdottir
Spiez Laboratory, Austrasse, 3700 Spiez, Switzerland

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Brief report
Published: 12 February 2021 in Viruses
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Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

ACS Style

Hulda R. Jonsdottir; Michel Bielecki; Denise Siegrist; Thomas W. Buehrer; Roland Züst; Jeremy W. Deuel. Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults. Viruses 2021, 13, 284 .

AMA Style

Hulda R. Jonsdottir, Michel Bielecki, Denise Siegrist, Thomas W. Buehrer, Roland Züst, Jeremy W. Deuel. Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults. Viruses. 2021; 13 (2):284.

Chicago/Turabian Style

Hulda R. Jonsdottir; Michel Bielecki; Denise Siegrist; Thomas W. Buehrer; Roland Züst; Jeremy W. Deuel. 2021. "Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults." Viruses 13, no. 2: 284.

Author correction
Published: 09 November 2020 in Virology Journal
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An amendment to this paper has been published and can be accessed via the original article. The conclusions of this paper have been corroborated by additional data.

ACS Style

Johanna Signer; Hulda R. Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. Author Correction: In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2. Virology Journal 2020, 17, 1 -4.

AMA Style

Johanna Signer, Hulda R. Jonsdottir, Werner C. Albrich, Marc Strasser, Roland Züst, Sarah Ryter, Rahel Ackermann-Gäumann, Nicole Lenz, Denise Siegrist, Andreas Suter, Roland Schoop, Olivier B. Engler. Author Correction: In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2. Virology Journal. 2020; 17 (1):1-4.

Chicago/Turabian Style

Johanna Signer; Hulda R. Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. 2020. "Author Correction: In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2." Virology Journal 17, no. 1: 1-4.

Research
Published: 21 September 2020 in Virology Journal
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Background Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but outbreaks of Middle East Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV-1, and the recently identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 4 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections. Therefore we investigated the virucidal and antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E, highly pathogenic MERS- and SARS-CoVs, as well as the newly identified SARS-CoV-2, in vitro. Methods To evaluate the antiviral potential of the extract, we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract after infection to further evaluate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce® in re-constituted nasal epithelium. Results In the current study, we found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce® at 3.2 μg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 μg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. The observed virucidal activity of Echinaforce® was not restricted to common cold coronaviruses, as both SARS-CoV-1 and MERS-CoVs were inactivated at comparable concentrations. Finally, the causative agent of COVID-19, SARS-CoV-2 was also inactivated upon treatment with 50μg/ml Echinaforce®. Conclusions These results show that Echinaforce® is virucidal against HCoV-229E, upon direct contact and in an organotypic cell culture model. Furthermore, MERS-CoV and both SARS-CoV-1 and SARS-CoV-2 were inactivated at similar concentrations of the extract. Therefore we hypothesize that Echinacea purpurea preparations, such as Echinaforce®, could be effective as prophylactic treatment for all CoVs due to their structural similarities.

ACS Style

Johanna Signer; Hulda R. Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2. Virology Journal 2020, 17, 1 -11.

AMA Style

Johanna Signer, Hulda R. Jonsdottir, Werner C. Albrich, Marc Strasser, Roland Züst, Sarah Ryter, Rahel Ackermann-Gäumann, Nicole Lenz, Denise Siegrist, Andreas Suter, Roland Schoop, Olivier B. Engler. In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2. Virology Journal. 2020; 17 (1):1-11.

Chicago/Turabian Style

Johanna Signer; Hulda R. Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. 2020. "In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2." Virology Journal 17, no. 1: 1-11.

Preprint content
Published: 15 August 2020
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Background: Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but outbreaks of Middle Eastern Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV, and the recently identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 4 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections.Therefore we investigated the virucidal and antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E, highly pathogenic MERS- and SARS-CoVs, as well as the newly identified SARS-CoV-2, in vitro.Methods: To evaluate the antiviral potential of the extract we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract after infection to further evaluate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce® in re-constituted nasal epithelium.Results: In the current study, we found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce® at 3.2mg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 mg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. The observed virucidal activity of Echinaforce® was not restricted to common cold coronaviruses, as both SARS-CoV-1 and MERS-CoVs were inactivated at comparable concentrations. Finally, the causative agent of COVID-19, SARS-CoV-2 was also inactivated upon treatment with 50ug/ml Echinaforce®.Conclusions: These results show that Echinaforce® is virucidal against HCoV-229E, upon direct contact and in an organotypic cell culture model. Furthermore, MERS-CoV and both SARS-CoV-1 and SARS-CoV-2 were inactivated at similar concentrations of the extract. Therefore we hypothesize that Echinacea purpurea preparations, such as Echinaforce®, could be effective as prophylactic treatment for all CoVs due to their structural similarities.

ACS Style

Johanna Signer; Hulda R. Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2. 2020, 1 .

AMA Style

Johanna Signer, Hulda R. Jonsdottir, Werner C. Albrich, Marc Strasser, Roland Züst, Sarah Ryter, Rahel Ackermann-Gäumann, Nicole Lenz, Denise Siegrist, Andreas Suter, Roland Schoop, Olivier B. Engler. In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2. . 2020; ():1.

Chicago/Turabian Style

Johanna Signer; Hulda R. Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. 2020. "In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2." , no. : 1.

Preprint content
Published: 10 March 2020
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Background: Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but recent outbreaks of Middle Eastern Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV, and the newly identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 2 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections and therefore we investigated the antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E and the highly pathogenic MERS- and SARS-CoVs in vitro.Methods:To evaluate the antiviral potential of Echinaforce we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract post-infection to further estimate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce in re-constituted nasal epithelium.Results:We found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce at 3.2mg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 mg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. Finally, antiviral activity was not restricted to common cold coronaviruses, as the highly pathogenic SARS- and MERS-CoVs were inactivated at comparable concentrations.Conclusions:These results suggest that Echinacea purpurea preparations, such as Echinaforce, could be effective as prophylactic treatment for all CoVs, including newly occurring strains, such as SARS-CoV-2.

ACS Style

Johanna Signer; Hulda Run Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. In vitro antiviral activity of Echinaforce®, an Echinacea purpurea preparation, against common cold coronavirus 229E and highly pathogenic MERS-CoV and SARS-CoV. 2020, 1 .

AMA Style

Johanna Signer, Hulda Run Jonsdottir, Werner C. Albrich, Marc Strasser, Roland Züst, Sarah Ryter, Rahel Ackermann-Gäumann, Nicole Lenz, Denise Siegrist, Andreas Suter, Roland Schoop, Olivier B. Engler. In vitro antiviral activity of Echinaforce®, an Echinacea purpurea preparation, against common cold coronavirus 229E and highly pathogenic MERS-CoV and SARS-CoV. . 2020; ():1.

Chicago/Turabian Style

Johanna Signer; Hulda Run Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. 2020. "In vitro antiviral activity of Echinaforce®, an Echinacea purpurea preparation, against common cold coronavirus 229E and highly pathogenic MERS-CoV and SARS-CoV." , no. : 1.

Preprint content
Published: 26 February 2020
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Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but recent outbreaks of Middle Eastern Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV, and the newly identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 2 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections and therefore we investigated the antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E and the highly pathogenic MERS- and SARS-CoVs in vitro. We found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce at 3.2µg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 µg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. Finally, antiviral activity was not restricted to common cold coronaviruses, as the highly pathogenic SARS- and MERS-CoVs were inactivated at comparable concentrations. These results suggest that Echinacea purpurea preparations, such as Echinaforce, could be effective as prophylactic treatment for all CoVs, including newly occurring strains, such as SARS-CoV-2.

ACS Style

Johanna Signer; Hulda R. Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. In vitro antiviral activity of Echinaforce®, an Echinacea purpurea preparation, against common cold coronavirus 229E and highly pathogenic MERS-CoV and SARS-CoV. 2020, 1 .

AMA Style

Johanna Signer, Hulda R. Jonsdottir, Werner C. Albrich, Marc Strasser, Roland Züst, Sarah Ryter, Rahel Ackermann-Gäumann, Nicole Lenz, Denise Siegrist, Andreas Suter, Roland Schoop, Olivier B. Engler. In vitro antiviral activity of Echinaforce®, an Echinacea purpurea preparation, against common cold coronavirus 229E and highly pathogenic MERS-CoV and SARS-CoV. . 2020; ():1.

Chicago/Turabian Style

Johanna Signer; Hulda R. Jonsdottir; Werner C. Albrich; Marc Strasser; Roland Züst; Sarah Ryter; Rahel Ackermann-Gäumann; Nicole Lenz; Denise Siegrist; Andreas Suter; Roland Schoop; Olivier B. Engler. 2020. "In vitro antiviral activity of Echinaforce®, an Echinacea purpurea preparation, against common cold coronavirus 229E and highly pathogenic MERS-CoV and SARS-CoV." , no. : 1.

Journal article
Published: 13 August 2019 in Viruses
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Primary human airway epithelial cell (hAEC) cultures represent a universal platform to propagate respiratory viruses and characterize their host interactions in authentic target cells. To further elucidate specific interactions between human respiratory viruses and important host factors in the airway epithelium, it is important to make hAEC cultures amenable to genetic modification. However, the short and finite lifespan of primary cells in cell culture creates a bottleneck for the genetic modification of these cultures. In the current study, we show that the incorporation of the Rho-associated protein kinase (ROCK) inhibitor (Y-27632) during cell propagation extends the life span of primary human cells in vitro and thereby facilitates the incorporation of lentivirus-based expression systems. Using fluorescent reporters for fluorescence-activated cell sorting (FACS)-based sorting, we generated homogenously fluorescent hAEC cultures that differentiate normally after lentiviral transduction. As a proof-of-principle, we demonstrate that host gene expression can be modulated post-differentiation via inducible short hairpin (sh)RNA-mediated knockdown. Importantly, functional characterization of these transgenic hAEC cultures with exogenous poly (I:C), as a proxy for virus infection, demonstrates that such modifications do not influence the host innate immune response. Moreover, the propagation kinetics of both human coronavirus 229E (HCoV-229E) and human respiratory syncytial virus (hRSV) were not affected. Combined, these results validate our newly established protocol for the genetic modification of hAEC cultures, thereby unlocking a unique potential for detailed molecular characterization of virus–host interactions in human respiratory epithelium.

ACS Style

Hulda R. Jonsdottir; Sabrina Marti; Dirk Geerts; Regulo Rodriguez; Volker Thiel; Ronald Dijkman. Establishment of Primary Transgenic Human Airway Epithelial Cell Cultures to Study Respiratory Virus–Host Interactions. Viruses 2019, 11, 747 .

AMA Style

Hulda R. Jonsdottir, Sabrina Marti, Dirk Geerts, Regulo Rodriguez, Volker Thiel, Ronald Dijkman. Establishment of Primary Transgenic Human Airway Epithelial Cell Cultures to Study Respiratory Virus–Host Interactions. Viruses. 2019; 11 (8):747.

Chicago/Turabian Style

Hulda R. Jonsdottir; Sabrina Marti; Dirk Geerts; Regulo Rodriguez; Volker Thiel; Ronald Dijkman. 2019. "Establishment of Primary Transgenic Human Airway Epithelial Cell Cultures to Study Respiratory Virus–Host Interactions." Viruses 11, no. 8: 747.

Journal article
Published: 05 March 2019 in Communications Biology
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Aircraft emissions contribute to local and global air pollution. Health effects of particulate matter (PM) from aircraft engines are largely unknown, since controlled cell exposures at relevant conditions are challenging. We examined the toxicity of non-volatile PM (nvPM) emissions from a CFM56-7B26 turbofan, the world’s most used aircraft turbine using an unprecedented exposure setup. We combined direct turbine-exhaust sampling under realistic engine operating conditions and the Nano-Aerosol Chamber for In vitro Toxicity to deposit particles onto air–liquid-interface cultures of human bronchial epithelial cells (BEAS-2B) at physiological conditions. We evaluated acute cellular responses after 1-h exposures to diluted exhaust from conventional or alternative fuel combustion. We show that single, short-term exposures to nvPM impair bronchial epithelial cells, and PM from conventional fuel at ground-idle conditions is the most hazardous. Electron microscopy of soot reveals varying reactivity matching the observed cellular responses. Stronger responses at lower mass concentrations suggest that additional metrics are necessary to evaluate health risks of this increasingly important emission source. Hulda R. Jonsdottir et al. examine the effects of non-volatile particulate matter from an aircraft turbine to cultures of human bronchial epithelial cells. They find that short-term exposures to exhaust particles cause cytotoxicity, oxidative stress, and immune infiltration, highlighting the need for further study into the effects of jet fuel-derived pollution.

ACS Style

Hulda R. Jonsdottir; Mathilde Delaval; Zaira Leni; Alejandro Keller; Benjamin T. Brem; Frithjof Siegerist; David Schönenberger; Lukas Durdina; Miriam Elser; Heinz Burtscher; Anthi Liati; Marianne Geiser. Non-volatile particle emissions from aircraft turbine engines at ground-idle induce oxidative stress in bronchial cells. Communications Biology 2019, 2, 1 -11.

AMA Style

Hulda R. Jonsdottir, Mathilde Delaval, Zaira Leni, Alejandro Keller, Benjamin T. Brem, Frithjof Siegerist, David Schönenberger, Lukas Durdina, Miriam Elser, Heinz Burtscher, Anthi Liati, Marianne Geiser. Non-volatile particle emissions from aircraft turbine engines at ground-idle induce oxidative stress in bronchial cells. Communications Biology. 2019; 2 (1):1-11.

Chicago/Turabian Style

Hulda R. Jonsdottir; Mathilde Delaval; Zaira Leni; Alejandro Keller; Benjamin T. Brem; Frithjof Siegerist; David Schönenberger; Lukas Durdina; Miriam Elser; Heinz Burtscher; Anthi Liati; Marianne Geiser. 2019. "Non-volatile particle emissions from aircraft turbine engines at ground-idle induce oxidative stress in bronchial cells." Communications Biology 2, no. 1: 1-11.

Journal article
Published: 22 January 2019 in Environmental Pollution
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Aircraft soot has a significant impact on global and local air pollution and is of particular concern for the population working at airports and living nearby. The morphology and chemistry of soot are related to its reactivity and depend mainly on engine operating conditions and fuel-type. We investigated the morphology (by transmission electron microscopy) and chemistry (by X-ray micro-spectroscopy) of soot from the exhaust of a CFM 56-7B26 turbofan engine, currently the most common engine in aviation fleet, operated in the test cell of SR Technics, Zurich airport. Standard kerosene (Jet A-1) and an alternative fuel blend (Jet A-1 with 32% HEFA) were used at ground idle and climb-out engine thrust, as these conditions highly influence air quality at airport areas. The results indicate that soot reactivity decreases from ground idle to climb-out conditions for both fuel types. Nearly one third of the primary soot particles generated by the blended fuel at climb-out engine thrust bear an outer amorphous shell implying higher reactivity. This characteristic referring to soot reactivity needs to be taken into account when evaluating the advantage of HEFA blending at high engine thrust. The soot type that is most prone to react with its surrounding is generated by Jet A-1 fuel at ground idle. Alternative fuel blending slightly lowers soot reactivity at ground idle but does the opposite at climb-out conditions. As far as soot reactivity is concerned, alternative fuels can prove beneficial for airports where ground idle is a common situation; the benefit of alternative fuels for climb-out conditions is uncertain.

ACS Style

A. Liati; D. Schreiber; Peter Alpert; Y. Liao; B.T. Brem; P. Corral Arroyo; J. Hu; Hulda R. Jonsdottir; M. Ammann; P. Dimopoulos Eggenschwiler. Aircraft soot from conventional fuels and biofuels during ground idle and climb-out conditions: Electron microscopy and X-ray micro-spectroscopy. Environmental Pollution 2019, 247, 658 -667.

AMA Style

A. Liati, D. Schreiber, Peter Alpert, Y. Liao, B.T. Brem, P. Corral Arroyo, J. Hu, Hulda R. Jonsdottir, M. Ammann, P. Dimopoulos Eggenschwiler. Aircraft soot from conventional fuels and biofuels during ground idle and climb-out conditions: Electron microscopy and X-ray micro-spectroscopy. Environmental Pollution. 2019; 247 ():658-667.

Chicago/Turabian Style

A. Liati; D. Schreiber; Peter Alpert; Y. Liao; B.T. Brem; P. Corral Arroyo; J. Hu; Hulda R. Jonsdottir; M. Ammann; P. Dimopoulos Eggenschwiler. 2019. "Aircraft soot from conventional fuels and biofuels during ground idle and climb-out conditions: Electron microscopy and X-ray micro-spectroscopy." Environmental Pollution 247, no. : 658-667.

Journal article
Published: 15 August 2016 in Proceedings of the National Academy of Sciences
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The four human coronaviruses (HCoVs) are globally endemic respiratory pathogens. The Middle East respiratory syndrome (MERS) coronavirus (CoV) is an emerging CoV with a known zoonotic source in dromedary camels. Little is known about the origins of endemic HCoVs. Studying these viruses’ evolutionary history could provide important insight into CoV emergence. In tests of MERS-CoV–infected dromedaries, we found viruses related to an HCoV, known as HCoV-229E, in 5.6% of 1,033 animals. Human- and dromedary-derived viruses are each monophyletic, suggesting ecological isolation. One gene of dromedary viruses exists in two versions in camels, full length and deleted, whereas only the deleted version exists in humans. The deletion increased in size over a succession starting from camelid viruses via old human viruses to contemporary human viruses. Live isolates of dromedary 229E viruses were obtained and studied to assess human infection risks. The viruses used the human entry receptor aminopeptidase N and replicated in human hepatoma cells, suggesting a principal ability to cause human infections. However, inefficient replication in several mucosa-derived cell lines and airway epithelial cultures suggested lack of adaptation to the human host. Dromedary viruses were as sensitive to the human type I interferon response as HCoV-229E. Antibodies in human sera neutralized dromedary-derived viruses, suggesting population immunity against dromedary viruses. Although no current epidemic risk seems to emanate from these viruses, evolutionary inference suggests that the endemic human virus HCoV-229E may constitute a descendant of camelid-associated viruses. HCoV-229E evolution provides a scenario for MERS-CoV emergence.

ACS Style

Victor M. Corman; Isabella Eckerle; Ziad A. Memish; Anne M. Liljander; Ronald Dijkman; Hulda R. Jonsdottir; Kisi J. Z. Juma Ngeiywa; Esther Kamau; Mario Younan; Malakita Al Masri; Abdullah Assiri; Ilona Gluecks; Bakri E. Musa; Benjamin Meyer; Marcel A. Müller; Mosaad A. Hilali; Set Bornstein; Ulrich Wernery; Volker Thiel; Joerg Jores; Jan Felix Drexler; Christian Drosten. Link of a ubiquitous human coronavirus to dromedary camels. Proceedings of the National Academy of Sciences 2016, 113, 9864 -9869.

AMA Style

Victor M. Corman, Isabella Eckerle, Ziad A. Memish, Anne M. Liljander, Ronald Dijkman, Hulda R. Jonsdottir, Kisi J. Z. Juma Ngeiywa, Esther Kamau, Mario Younan, Malakita Al Masri, Abdullah Assiri, Ilona Gluecks, Bakri E. Musa, Benjamin Meyer, Marcel A. Müller, Mosaad A. Hilali, Set Bornstein, Ulrich Wernery, Volker Thiel, Joerg Jores, Jan Felix Drexler, Christian Drosten. Link of a ubiquitous human coronavirus to dromedary camels. Proceedings of the National Academy of Sciences. 2016; 113 (35):9864-9869.

Chicago/Turabian Style

Victor M. Corman; Isabella Eckerle; Ziad A. Memish; Anne M. Liljander; Ronald Dijkman; Hulda R. Jonsdottir; Kisi J. Z. Juma Ngeiywa; Esther Kamau; Mario Younan; Malakita Al Masri; Abdullah Assiri; Ilona Gluecks; Bakri E. Musa; Benjamin Meyer; Marcel A. Müller; Mosaad A. Hilali; Set Bornstein; Ulrich Wernery; Volker Thiel; Joerg Jores; Jan Felix Drexler; Christian Drosten. 2016. "Link of a ubiquitous human coronavirus to dromedary camels." Proceedings of the National Academy of Sciences 113, no. 35: 9864-9869.

Review
Published: 06 February 2016 in Virology Journal
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Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition.

ACS Style

Hulda R. Jonsdottir; Ronald Dijkman. Coronaviruses and the human airway: a universal system for virus-host interaction studies. Virology Journal 2016, 13, 1 -9.

AMA Style

Hulda R. Jonsdottir, Ronald Dijkman. Coronaviruses and the human airway: a universal system for virus-host interaction studies. Virology Journal. 2016; 13 (1):1-9.

Chicago/Turabian Style

Hulda R. Jonsdottir; Ronald Dijkman. 2016. "Coronaviruses and the human airway: a universal system for virus-host interaction studies." Virology Journal 13, no. 1: 1-9.

Journal article
Published: 21 September 2015 in Laboratory Investigation
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Laboratory Investigation is the official journal of the United States and Canadian Academy of Pathology. Laboratory Investigation is available as both in print and online journal and is dedicated to the publication of original research that significantly advances the understanding of human and experimental disease including basic biology papers with a relevance to experimental or clinical aspects of disease. The journal also publishes papers detailing relevant advances in technical methodology.

ACS Style

Hulda R. Jonsdottir; Ari Jon Arason; Ragnar Palsson; Sigridur Rut Franzdottir; Tomas Gudbjartsson; Helgi J Isaksson; Gunnar Gudmundsson; Thorarinn Gudjonsson; Magnus Karl Magnusson. Basal cells of the human airways acquire mesenchymal traits in idiopathic pulmonary fibrosis and in culture. Laboratory Investigation 2015, 95, 1418 -1428.

AMA Style

Hulda R. Jonsdottir, Ari Jon Arason, Ragnar Palsson, Sigridur Rut Franzdottir, Tomas Gudbjartsson, Helgi J Isaksson, Gunnar Gudmundsson, Thorarinn Gudjonsson, Magnus Karl Magnusson. Basal cells of the human airways acquire mesenchymal traits in idiopathic pulmonary fibrosis and in culture. Laboratory Investigation. 2015; 95 (12):1418-1428.

Chicago/Turabian Style

Hulda R. Jonsdottir; Ari Jon Arason; Ragnar Palsson; Sigridur Rut Franzdottir; Tomas Gudbjartsson; Helgi J Isaksson; Gunnar Gudmundsson; Thorarinn Gudjonsson; Magnus Karl Magnusson. 2015. "Basal cells of the human airways acquire mesenchymal traits in idiopathic pulmonary fibrosis and in culture." Laboratory Investigation 95, no. 12: 1418-1428.

Book chapter
Published: 12 February 2015 in Methods in Molecular Biology
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The human airway serves as the entry point of human respiratory viruses, including human coronaviruses. In this chapter we outline the methods by which we establish fully differentiated airway epithelium and its use for human coronavirus propagation. Additionally, we outline methods for immunofluorescence staining of these cultures for virus detection, characterization of cell tropism, and how to perform antiviral assays and quantify viral replication.

ACS Style

Hulda R. Jonsdottir; Ronald Dijkman. Characterization of Human Coronaviruses on Well-Differentiated Human Airway Epithelial Cell Cultures. Methods in Molecular Biology 2015, 73 -87.

AMA Style

Hulda R. Jonsdottir, Ronald Dijkman. Characterization of Human Coronaviruses on Well-Differentiated Human Airway Epithelial Cell Cultures. Methods in Molecular Biology. 2015; ():73-87.

Chicago/Turabian Style

Hulda R. Jonsdottir; Ronald Dijkman. 2015. "Characterization of Human Coronaviruses on Well-Differentiated Human Airway Epithelial Cell Cultures." Methods in Molecular Biology , no. : 73-87.

Research article
Published: 29 May 2014 in PLOS Pathogens
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Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections. Viruses that replicate in the host cell cytoplasm have evolved to employ host cell-derived membranes to compartmentalize genome replication and transcription. Specifically for positive-stranded RNA viruses, accumulating knowledge concerning the involvement, rearrangement and requirement of cellular membranes for RNA synthesis specify the establishment of the viral replicase complex at host cell-derived membranes as an evolutionary conserved and essential step in the early phase of the viral life cycle. Here we describe a small compound inhibitor of coronavirus replication that (i) specifically targets this membrane-bound RNA replication step and (ii) has broad antiviral activity against number of diverse coronaviruses including highly pathogenic SARS-CoV and MERS-CoV. Since resistance mutations appear in an integral membrane-spanning component of the coronavirus replicase complex, and since all positive stranded RNA viruses have very similar membrane-spanning or membrane-associated replicase components implicated in anchoring the viral replication complex to host cell-derived membranes, our data suggest that the membrane-bound replication step of the viral life cycle is a novel, vulnerable, and druggable target for antiviral intervention of a wide range of RNA virus infections.

ACS Style

Anna Lundin; Ronald Dijkman; Tomas Bergström; Nina Kann; Beata Adamiak; Charles Hannoun; Eveline Kindler; Hulda R. Jonsdottir; Doreen Muth; Joeri Kint; Maria Forlenza; Marcel A. Müller; Christian Drosten; Volker Thiel; Edward Trybala. Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus. PLOS Pathogens 2014, 10, e1004166 .

AMA Style

Anna Lundin, Ronald Dijkman, Tomas Bergström, Nina Kann, Beata Adamiak, Charles Hannoun, Eveline Kindler, Hulda R. Jonsdottir, Doreen Muth, Joeri Kint, Maria Forlenza, Marcel A. Müller, Christian Drosten, Volker Thiel, Edward Trybala. Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus. PLOS Pathogens. 2014; 10 (5):e1004166.

Chicago/Turabian Style

Anna Lundin; Ronald Dijkman; Tomas Bergström; Nina Kann; Beata Adamiak; Charles Hannoun; Eveline Kindler; Hulda R. Jonsdottir; Doreen Muth; Joeri Kint; Maria Forlenza; Marcel A. Müller; Christian Drosten; Volker Thiel; Edward Trybala. 2014. "Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus." PLOS Pathogens 10, no. 5: e1004166.

Research article
Published: 12 February 2014 in PLOS ONE
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The upper airways are lined with a pseudostratified bronchial epithelium that forms a barrier against unwanted substances in breathing air. The transcription factor p63, which is important for stratification of skin epithelium, has been shown to be expressed in basal cells of the lungs and its ΔN isoform is recognized as a key player in squamous cell lung cancer. However, the role of p63 in formation and maintenance of bronchial epithelia is largely unknown. The objective of the current study was to determine the expression pattern of the ΔN and TA isoforms of p63 and the role of p63 in the development and maintenance of pseudostratified lung epithelium in situ and in culture. We used a human bronchial epithelial cell line with basal cell characteristics (VA10) to model bronchial epithelium in an air-liquid interface culture (ALI) and performed a lentiviral-based silencing of p63 to characterize the functional and phenotypic consequences of p63 loss. We demonstrate that ΔNp63 is the major isoform in the human lung and its expression was exclusively found in the basal cells lining the basement membrane of the bronchial epithelium. Knockdown of p63 affected proliferation and migration of VA10 cells and facilitated cellular senescence. Expression of p63 is critical for epithelial repair as demonstrated by wound healing assays. Importantly, generation of pseudostratified VA10 epithelium in the ALI setup depended on p63 expression and goblet cell differentiation, which can be induced by IL-13 stimulation, was abolished by the p63 knockdown. After knockdown of p63 in primary bronchial epithelial cells they did not proliferate and showed marked senescence. We conclude that these results strongly implicate p63 in the formation and maintenance of differentiated pseudostratified bronchial epithelium.

ACS Style

Ari Jon Arason; Hulda R. Jonsdottir; Skarphedinn Halldorsson; Berglind Eva Benediktsdóttir; Jon Thor Bergthorsson; Saevar Ingthorsson; Olafur Baldursson; Satrajit Sinha; Thorarinn Gudjonsson; Magnus Karl Magnusson. deltaNp63 Has a Role in Maintaining Epithelial Integrity in Airway Epithelium. PLOS ONE 2014, 9, e88683 .

AMA Style

Ari Jon Arason, Hulda R. Jonsdottir, Skarphedinn Halldorsson, Berglind Eva Benediktsdóttir, Jon Thor Bergthorsson, Saevar Ingthorsson, Olafur Baldursson, Satrajit Sinha, Thorarinn Gudjonsson, Magnus Karl Magnusson. deltaNp63 Has a Role in Maintaining Epithelial Integrity in Airway Epithelium. PLOS ONE. 2014; 9 (2):e88683.

Chicago/Turabian Style

Ari Jon Arason; Hulda R. Jonsdottir; Skarphedinn Halldorsson; Berglind Eva Benediktsdóttir; Jon Thor Bergthorsson; Saevar Ingthorsson; Olafur Baldursson; Satrajit Sinha; Thorarinn Gudjonsson; Magnus Karl Magnusson. 2014. "deltaNp63 Has a Role in Maintaining Epithelial Integrity in Airway Epithelium." PLOS ONE 9, no. 2: e88683.

Observation
Published: 01 March 2013 in mBio
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The recent emergence of a novel human coronavirus (HCoV-EMC) in the Middle East raised considerable concerns, as it is associated with severe acute pneumonia, renal failure, and fatal outcome and thus resembles the clinical presentation of severe acute respiratory syndrome (SARS) observed in 2002 and 2003. Like SARS-CoV, HCoV-EMC is of zoonotic origin and closely related to bat coronaviruses. The human airway epithelium (HAE) represents the entry point and primary target tissue for respiratory viruses and is highly relevant for assessing the zoonotic potential of emerging respiratory viruses, such as HCoV-EMC. Here, we show that pseudostratified HAE cultures derived from different donors are highly permissive to HCoV-EMC infection, and by using reverse transcription (RT)-PCR and RNAseq data, we experimentally determined the identity of seven HCoV-EMC subgenomic mRNAs. Although the HAE cells were readily responsive to type I and type III interferon (IFN), we observed neither a pronounced inflammatory cytokine nor any detectable IFN responses following HCoV-EMC, SARS-CoV, or HCoV-229E infection, suggesting that innate immune evasion mechanisms and putative IFN antagonists of HCoV-EMC are operational in the new host. Importantly, however, we demonstrate that both type I and type III IFN can efficiently reduce HCoV-EMC replication in HAE cultures, providing a possible treatment option in cases of suspected HCoV-EMC infection. IMPORTANCE A novel human coronavirus, HCoV-EMC, has recently been described to be associated with severe respiratory tract infection and fatalities, similar to severe acute respiratory syndrome (SARS) observed during the 2002-2003 epidemic. Closely related coronaviruses replicate in bats, suggesting that, like SARS-CoV, HCoV-EMC is of zoonotic origin. Since the animal reservoir and circumstances of zoonotic transmission are yet elusive, it is critically important to assess potential species barriers of HCoV-EMC infection. An important first barrier against invading respiratory pathogens is the epithelium, representing the entry point and primary target tissue of respiratory viruses. We show that human bronchial epithelia are highly susceptible to HCoV-EMC infection. Furthermore, HCoV-EMC, like other coronaviruses, evades innate immune recognition, reflected by the lack of interferon and minimal inflammatory cytokine expression following infection. Importantly, type I and type III interferon treatment can efficiently reduce HCoV-EMC replication in the human airway epithelium, providing a possible avenue for treatment of emerging virus infections.

ACS Style

Eveline Kindler; Hulda R. Jonsdottir; Doreen Muth; Ole J. Hamming; Rune Hartmann; Regulo Rodriguez; Robert Geffers; Ron Fouchier; Christian Drosten; Marcel A. Müller; Ronald Dijkman; Volker Thiel. Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential. mBio 2013, 4, e00611 -12.

AMA Style

Eveline Kindler, Hulda R. Jonsdottir, Doreen Muth, Ole J. Hamming, Rune Hartmann, Regulo Rodriguez, Robert Geffers, Ron Fouchier, Christian Drosten, Marcel A. Müller, Ronald Dijkman, Volker Thiel. Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential. mBio. 2013; 4 (1):e00611-12.

Chicago/Turabian Style

Eveline Kindler; Hulda R. Jonsdottir; Doreen Muth; Ole J. Hamming; Rune Hartmann; Regulo Rodriguez; Robert Geffers; Ron Fouchier; Christian Drosten; Marcel A. Müller; Ronald Dijkman; Volker Thiel. 2013. "Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential." mBio 4, no. 1: e00611-12.

Journal article
Published: 20 February 2013 in Journal of Virology
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The human airway epithelium (HAE) represents the entry port of many human respiratory viruses, including human coronaviruses (HCoVs). Nowadays, four HCoVs, HCoV-229E, HCoV-OC43, HCoV-HKU1, and HCoV-NL63, are known to be circulating worldwide, causing upper and lower respiratory tract infections in nonhospitalized and hospitalized children. Studies of the fundamental aspects of these HCoV infections at the primary entry port, such as cell tropism, are seriously hampered by the lack of a universal culture system or suitable animal models. To expand the knowledge on fundamental virus-host interactions for all four HCoVs at the site of primary infection, we used pseudostratified HAE cell cultures to isolate and characterize representative clinical HCoV strains directly from nasopharyngeal material. Ten contemporary isolates were obtained, representing HCoV-229E (n = 1), HCoV-NL63 (n = 1), HCoV-HKU1 (n = 4), and HCoV-OC43 (n = 4). For each strain, we analyzed the replication kinetics and progeny virus release on HAE cell cultures derived from different donors. Surprisingly, by visualizing HCoV infection by confocal microscopy, we observed that HCoV-229E employs a target cell tropism for nonciliated cells, whereas HCoV-OC43, HCoV-HKU1, and HCoV-NL63 all infect ciliated cells. Collectively, the data demonstrate that HAE cell cultures, which morphologically and functionally resemble human airways in vivo, represent a robust universal culture system for isolating and comparing all contemporary HCoV strain

ACS Style

R. Dijkman; M. F. Jebbink; S. M. Koekkoek; M. Deijs; Hulda R. Jonsdottir; R. Molenkamp; M. Ieven; H. Goossens; Volker Thiel; L. Van Der Hoek. Isolation and Characterization of Current Human Coronavirus Strains in Primary Human Epithelial Cell Cultures Reveal Differences in Target Cell Tropism. Journal of Virology 2013, 87, 6081 -6090.

AMA Style

R. Dijkman, M. F. Jebbink, S. M. Koekkoek, M. Deijs, Hulda R. Jonsdottir, R. Molenkamp, M. Ieven, H. Goossens, Volker Thiel, L. Van Der Hoek. Isolation and Characterization of Current Human Coronavirus Strains in Primary Human Epithelial Cell Cultures Reveal Differences in Target Cell Tropism. Journal of Virology. 2013; 87 (11):6081-6090.

Chicago/Turabian Style

R. Dijkman; M. F. Jebbink; S. M. Koekkoek; M. Deijs; Hulda R. Jonsdottir; R. Molenkamp; M. Ieven; H. Goossens; Volker Thiel; L. Van Der Hoek. 2013. "Isolation and Characterization of Current Human Coronavirus Strains in Primary Human Epithelial Cell Cultures Reveal Differences in Target Cell Tropism." Journal of Virology 87, no. 11: 6081-6090.