scholarly journals Middle East respiratory syndrome coronavirus shows poor replication but significant induction of antiviral responses in human monocyte-derived macrophages and dendritic cells

2016 ◽  
Vol 97 (2) ◽  
pp. 344-355 ◽  
Author(s):  
Janne Tynell ◽  
Veera Westenius ◽  
Esa Rönkkö ◽  
Vincent J. Munster ◽  
Krister Melén ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Middle East ◽  
Human Monocyte ◽  
Middle East Respiratory Syndrome ◽  
Antiviral Responses

scholarly journals Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 152 ◽  
Author(s):  
Arinjay Banerjee ◽  
Darryl Falzarano ◽  
Noreen Rapin ◽  
Jocelyne Lew ◽  
Vikram Misra
Keyword(s):  
Middle East ◽  
Nuclear Translocation ◽  
Human Cells ◽  
Middle East Respiratory Syndrome ◽  
Poly I:C ◽  
Interferon Response ◽  
Synthetic Analogue ◽  
Post Translational Modifications ◽  
Antiviral Responses ◽  
Interfering Rna

Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat (Eptesicus fuscus) cells with MERS-CoV and observed that the virus grew to higher titers in human cells. MERS-CoV also effectively suppressed the antiviral interferon beta (IFNβ) response in human cells, unlike in bat cells. To determine if IRF3, a critical mediator of the interferon response, also regulated the response in bats, we examined the response of IRF3 to poly(I:C), a synthetic analogue of viral double-stranded RNA. We observed that bat IRF3 responded to poly(I:C) by nuclear translocation and post-translational modifications, hallmarks of IRF3 activation. Suppression of IRF3 by small-interfering RNA (siRNA) demonstrated that IRF3 was critical for poly(I:C) and MERS-CoV induced induction of IFNβ in bat cells. Our study demonstrates that innate antiviral signaling in E. fuscus bat cells is resistant to MERS-CoV-mediated subversion.

scholarly journals High Secretion of Interferons by Human Plasmacytoid Dendritic Cells upon Recognition of Middle East Respiratory Syndrome Coronavirus

2015 ◽  
Vol 89 (7) ◽  
pp. 3859-3869 ◽  
Author(s):  
Vivian A. Scheuplein ◽  
Janna Seifried ◽  
Anna H. Malczyk ◽  
Lilija Miller ◽  
Lena Höcker ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Middle East ◽  
Respiratory Disease ◽  
Immune Cell ◽  
Critical Role ◽  
Plasmacytoid Dendritic Cells ◽  
Middle East Respiratory Syndrome ◽  
Early Gene ◽  
Type I ◽  
Endosomal Uptake

ABSTRACTThe Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as the causative agent of a severe respiratory disease with a fatality rate of approximately 30%. The high virulence and mortality rate prompted us to analyze aspects of MERS-CoV pathogenesis, especially its interaction with innate immune cells such as antigen-presenting cells (APCs). Particularly, we analyzed secretion of type I and type III interferons (IFNs) by APCs, i.e., B cells, macrophages, monocyte-derived/myeloid dendritic cells (MDDCs/mDCs), and by plasmacytoid dendritic cells (pDCs) of human and murine origin after inoculation with MERS-CoV. Production of large amounts of type I and III IFNs was induced exclusively in human pDCs, which were significantly higher than IFN induction by severe acute respiratory syndrome (SARS)-CoV. Of note, IFNs were secreted in the absence of productive replication. However, receptor binding, endosomal uptake, and probably signaling via Toll-like receptor 7 (TLR7) were critical for sensing of MERS-CoV by pDCs. Furthermore, active transcription of MERS-CoV N RNA and subsequent N protein expression were evident in infected pDCs, indicating abortive infection. Taken together, our results point toward dipeptidyl peptidase 4 (DPP4)-dependent endosomal uptake and subsequent infection of human pDCs by MERS-CoV. However, the replication cycle is stopped after early gene expression. In parallel, human pDCs are potent IFN-producing cells upon MERS-CoV infection. Knowledge of such IFN responses supports our understanding of MERS-CoV pathogenesis and is critical for the choice of treatment options.IMPORTANCEMERS-CoV causes a severe respiratory disease with high fatality rates in human patients. Recently, confirmed human cases have increased dramatically in both number and geographic distribution. Understanding the pathogenesis of this highly pathogenic CoV is crucial for developing successful treatment strategies. This study elucidates the interaction of MERS-CoV with APCs and pDCs, particularly the induction of type I and III IFN secretion. Human pDCs are the immune cell population sensing MERS-CoV but secrete significantly larger amounts of IFNs, especially IFN-α, than in response to SARS-CoV. A model for molecular virus-host interactions is presented outlining IFN induction in pDCs. The massive IFN secretion upon contact suggests a critical role of this mechanism for the high degree of immune activation observed during MERS-CoV infection.

Massive Infektion und alveolare Schädigung der humanen Lunge durch das Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Pneumologie ◽  
2015 ◽  
Vol 69 (04) ◽  
Author(s):  
A Becher ◽  
J von Recum ◽  
K Schierhorn ◽  
T Wolff ◽  
M Tönnies ◽  
...  
Keyword(s):  
Middle East ◽  
Middle East Respiratory Syndrome

Aerogen übertragene Infektionskrankheiten bei Kindern auf Reisen

2018 ◽  
Vol 18 (06) ◽  
pp. 422-426
Author(s):  
C. Rau ◽  
J. Lindert ◽  
S. Kotsias-Konopelska ◽  
R. Kobbe
Keyword(s):  
Middle East ◽  
Middle East Respiratory Syndrome ◽  
Bakterielle Infektionen ◽  
Saisonale Influenza

ZusammenfassungErkrankungen der Atemwege gehören zu den häufigsten Gesundheitsproblemen von Kindern und treten regelhaft auch während und nach Reisen auf. Virale Atemwegsinfektionen können die Reisefähigkeit von Kindern – und damit auch ihren Angehörigen – ungünstig beeinflussen, beispielsweise durch Fieber, bronchiale Obstruktion und Schwierigkeiten beim Druckausgleich während des Fliegens durch Schwellungen und Sekretionen der Schleimhäute und der eustachi‘schen Röhre. Zu den reisemedizinisch relevanten aerogen übertragenen Krankheiten zählen neben banalen, viralen Erkältungen auch potenziell schwer verlaufende Viruserkrankungen, allen voran die saisonale Influenza und die Masern, sowie bakterielle Infektionen durch Meningokokken und die Tuberkulose. Gegen einige dieser Erkrankungen stehen effektive Impfstoffe zur Verfügung. Auch seltene, schwer verlaufende Atemwegsinfektionen, die unter bestimmten epidemiologischen Umständen außerhalb Europas erworben werden können, sollen im Folgenden exemplarisch an den Erkrankungen Middle East respiratory syndrome (MERS) und der Histoplasmose dargestellt werden.

Lead Molecule Prediction and Characterization for Designing MERS-CoV 3C-like Protease Inhibitors: An In silico Approach

2018 ◽  
Vol 15 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Md. Mostafijur Rahman ◽  
Md. Bayejid Hosen ◽  
M. Zakir Hossain Howlader ◽  
Yearul Kabir
Keyword(s):  
Binding Energy ◽  
Middle East ◽  
Virtual Screening ◽  
In Silico ◽  
Screening Method ◽  
Middle East Respiratory Syndrome ◽  
Cytochrome P450 Enzymes ◽  
Drug Molecules ◽  
Essential Enzyme ◽  
Reduced Toxicity

Background: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. </P><P> Methods: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method. Further, the compounds were validated through absorption, distribution, metabolism and excretion filtering. Results: Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3 compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining 7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a substrate of P-glycoprotein. Our predicted compounds may be capable of inhibiting 3C-like protease but need some further validation in wet lab.

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