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Article ; Online: Surveillance of endemic human Coronaviruses in Germany, 2019/2020

Barbara Biere / Djin-Ye Oh / Thorsten Wolff / Ralf Dürrwald

The Lancet Regional Health. Europe, Vol 11, Iss , Pp 100262- (2021)

2021

Keywords	Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Different populations of A(H1N1)pdm09 viruses in a patient with hemolytic-uremic syndrome

Yuguang Fu / Marianne Wedde / Sigrun Smola / Djin-Ye Oh / Thorsten Pfuhl / Jürgen Rissland / Michael Zemlin / Fidelis A. Flockerzi / Rainer M. Bohle / Andrea Thürmer / Susanne Duwe / Barbara Biere / Janine Reiche / Brunhilde Schweiger / Christin Mache / Thorsten Wolff / Georg Herrler / Ralf Dürrwald

International Journal of Medical Microbiology, Vol 314, Iss , Pp 151598- (2024)

2024

Abstract: Respiratory viral infections may have different impacts ranging from infection without symptoms to severe disease or even death though the reasons are not well characterized.A patient (age group 5–15 years) displaying symptoms of hemolytic uremic ... ...

Abstract	Respiratory viral infections may have different impacts ranging from infection without symptoms to severe disease or even death though the reasons are not well characterized.A patient (age group 5–15 years) displaying symptoms of hemolytic uremic syndrome died one day after hospitalization. qPCR, next generation sequencing, virus isolation, antigenic characterization, resistance analysis was performed and virus replication kinetics in well-differentiated airway cells were determined.Autopsy revealed hemorrhagic pneumonia as major pathological manifestation. Lung samples harbored a large population of A(H1N1)pdm09 viruses with the polymorphism H456H/Y in PB1 polymerase. The H456H/Y viruses replicated much faster to high viral titers than upper respiratory tract viruses in vitro. H456H/Y-infected air-liquid interface cultures of differentiated airway epithelial cells did reflect a more pronounced loss of ciliated cells. A different pattern of virus quasispecies was found in the upper airway samples where substitution S263S/F (HA1) was observed.The data support the notion that viral quasispecies had evolved locally in the lung to support high replicative fitness. This change may have initiated further pathogenic processes leading to rapid dissemination of inflammatory mediators followed by development of hemorrhagic lung lesions and fatal outcome.
Keywords	A(H1N1)pdm09 virus ; Fatal influenza ; S263S/F (HA1) and H456H/Y (PB1) mutations ; Microbiology ; QR1-502 ; Other systems of medicine ; RZ201-999
Language	English
Publishing date	2024-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Virological Surveillance and Molecular Characterization of Human Parainfluenzavirus Infection in Children with Acute Respiratory Illness

Djin-Ye Oh / Barbara Biere / Markus Grenz / Thorsten Wolff / Brunhilde Schweiger / Ralf Dürrwald / Janine Reiche

Microorganisms, Vol 9, Iss 1508, p

Germany, 2015–2019

2021 Volume 1508

Abstract: Human parainfluenza viruses (HPIVs) are important causes of respiratory illness, especially in young children. However, surveillance for HPIV is rarely performed continuously, and national-level epidemiologic and genetic data are scarce. Within the ... ...

Abstract	Human parainfluenza viruses (HPIVs) are important causes of respiratory illness, especially in young children. However, surveillance for HPIV is rarely performed continuously, and national-level epidemiologic and genetic data are scarce. Within the German sentinel system, to monitor acute respiratory infections (ARI), 4463 respiratory specimens collected from outpatients < 5 years of age between October 2015 and September 2019 were retrospectively screened for HPIV 1–4 using real-time PCR. HPIV was identified in 459 (10%) samples. HPIV-3 was the most common HPIV-type, with 234 detections, followed by HPIV-1 (113), HPIV-4 (61), and HPIV-2 (49). HPIV-3 was more frequently associated with age < 2 years, and HPIV-4 was more frequently associated with pneumonia compared to other HPIV types. HPIV circulation displayed distinct seasonal patterns, which appeared to vary by type. Phylogenetic characterization clustered HPIV-1 in Clades 2 and 3. Reclassification was performed for HPIV-2, provisionally assigning two distinct HPIV-2 groups and six clades, with German HPIV-2s clustering in Clade 2.4. HPIV-3 clustered in C1, C3, C5, and, interestingly, in A. HPIV-4 clustered in Clades 2.1 and 2.2. The results of this study may serve to inform future approaches to diagnose and prevent HPIV infections, which contribute substantially to ARI in young children in Germany.
Keywords	human parainfluenza virus ; orthorubulavirus ; respirovirus ; acute respiratory infection ; influenza-like illness ; croup ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 Omicron variant is attenuated for replication in a polarized human lung epithelial cell model

Christin Mache / Jessica Schulze / Gudrun Holland / Daniel Bourquain / Jean-Marc Gensch / Djin-Ye Oh / Andreas Nitsche / Ralf Dürrwald / Michael Laue / Thorsten Wolff

Communications Biology, Vol 5, Iss 1, Pp 1-

2022 Volume 8

Abstract: Human alveolar epithelial lentivirus immortalized cells are very permissive for human coronaviruses and influenza A viruses, provided a suitable model for such infections of the lower respiratory tract as shown by reduced propagation of the SARS-CoV-2 ... ...

Abstract	Human alveolar epithelial lentivirus immortalized cells are very permissive for human coronaviruses and influenza A viruses, provided a suitable model for such infections of the lower respiratory tract as shown by reduced propagation of the SARS-CoV-2 Omicron variant.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Adeno‐associated virus‐vectored influenza vaccine elicits neutralizing and Fcγ receptor‐activating antibodies

Daniel E Demminger / Lisa Walz / Kristina Dietert / Helen Hoffmann / Oliver Planz / Achim D Gruber / Veronika vonMessling / Thorsten Wolff

EMBO Molecular Medicine, Vol 12, Iss 5, Pp n/a-n/a (2020)

2020

Abstract: Abstract The current seasonal inactivated influenza vaccine protects only against a narrow range of virus strains as it triggers a dominant antibody response toward the hypervariable hemagglutinin (HA) head region. The discovery of rare broadly ... ...

Abstract	Abstract The current seasonal inactivated influenza vaccine protects only against a narrow range of virus strains as it triggers a dominant antibody response toward the hypervariable hemagglutinin (HA) head region. The discovery of rare broadly protective antibodies against conserved regions in influenza virus proteins has propelled research on distinct antigens and delivery methods to efficiently induce broad immunity toward drifted or shifted virus strains. Here, we report that adeno‐associated virus (AAV) vectors expressing influenza virus HA or chimeric HA protected mice against homologous and heterologous virus challenges. Unexpectedly, immunization even with wild‐type HA induced antibodies recognizing the HA‐stalk and activating FcγR‐dependent responses indicating that AAV‐vectored expression balances HA head‐ and HA stalk‐specific humoral responses. Immunization with AAV‐HA partially protected also ferrets against a harsh virus challenge. Results from this study provide a rationale for further clinical development of AAV vectors as influenza vaccine platform, which could benefit from their approved use in human gene therapy.
Keywords	adeno‐associated virus vector ; broadly reactive antibody ; FcγR ; HA stalk ; universal influenza vaccine ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
Subject code	616
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transcriptomic comparison of primary human lung cells with lung tissue samples and the human A549 lung cell line highlights cell type specific responses during infections with influenza A virus

Wilhelm Bertrams / Katja Hönzke / Benedikt Obermayer / Mario Tönnies / Torsten T. Bauer / Paul Schneider / Jens Neudecker / Jens C. Rückert / Thorsten Stiewe / Andrea Nist / Stephan Eggeling / Norbert Suttorp / Thorsten Wolff / Stefan Hippenstiel / Bernd Schmeck / Andreas C. Hocke

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 11

Abstract: Abstract Influenza A virus (IAV) causes pandemics and annual epidemics of severe respiratory infections. A better understanding of the molecular regulation in tissue and cells upon IAV infection is needed to thoroughly understand pathogenesis. We ... ...

Abstract	Abstract Influenza A virus (IAV) causes pandemics and annual epidemics of severe respiratory infections. A better understanding of the molecular regulation in tissue and cells upon IAV infection is needed to thoroughly understand pathogenesis. We analyzed IAV replication and gene expression induced by IAV strain H3N2 Panama in isolated primary human alveolar epithelial type II cells (AECIIs), the permanent A549 adenocarcinoma cell line, alveolar macrophages (AMs) and explanted human lung tissue by bulk RNA sequencing. Primary AECII exhibit in comparison to AM a broad set of strongly induced genes related to RIG-I and interferon (IFN) signaling. The response of AECII was partly mirrored in A549 cells. In human lung tissue, we observed induction of genes unlike in isolated cells. Viral RNA was used to correlate host cell gene expression changes with viral burden. While relative induction of key genes was similar, gene abundance was highest in AECII cells and AM, while weaker in the human lung (due to less IAV replication) and A549 cells (pointing to their limited suitability as a model). Correlation of host gene induction with viral burden allows a better understanding of the cell-type specific induction of pathways and a possible role of cellular crosstalk requiring intact tissue.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Activation of the Antiviral Kinase PKR and Viral Countermeasures

Bianca Dauber / Thorsten Wolff

Viruses, Vol 1, Iss 3, Pp 523-

2009 Volume 544

Abstract: The interferon-induced double-stranded (ds)RNA-dependent protein kinase (PKR) limits viral replication by an eIF2α-mediated block of translation. Although many negative-strand RNA viruses activate PKR, the responsible RNAs have long remained elusive, as ... ...

Abstract	The interferon-induced double-stranded (ds)RNA-dependent protein kinase (PKR) limits viral replication by an eIF2α-mediated block of translation. Although many negative-strand RNA viruses activate PKR, the responsible RNAs have long remained elusive, as dsRNA, the canonical activator of PKR, has not been detected in cells infected with such viruses. In this review we focus on the activating RNA molecules of different virus families, in particular the negative-strand RNA viruses. We discuss the recently identified non-canonical activators 5’-triphosphate RNA and the vRNP of influenza virus and give an update on strategies of selected RNA and DNA viruses to prevent activation of PKR.
Keywords	PKR ; virus ; dsRNA ; innate immunity ; immune evasion ; Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Language	English
Publishing date	2009-10-01T00:00:00Z
Publisher	Molecular Diversity Preservation International
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Highly pathogenic H5N1 influenza A virus strains provoke heterogeneous IFN-α/β responses that distinctively affect viral propagation in human cells.

Markus Matthaei / Matthias Budt / Thorsten Wolff

PLoS ONE, Vol 8, Iss 2, p e

2013 Volume 56659

Abstract: The fatal transmissions of highly pathogenic avian influenza A viruses (IAV) of the H5N1 subtype to humans and high titer replication in the respiratory tract indicate that these pathogens can overcome the bird-to-human species barrier. While type I ... ...

Abstract	The fatal transmissions of highly pathogenic avian influenza A viruses (IAV) of the H5N1 subtype to humans and high titer replication in the respiratory tract indicate that these pathogens can overcome the bird-to-human species barrier. While type I interferons (IFN-α/β) are well described to contribute to the species barrier of many zoonotic viruses, current data to the role of these antiviral cytokines during human H5N1 IAV infections is limited and contradictory. We hypothesized an important role for the IFN system in limiting productive infection of avian H5N1 strains in human cells. Hence, we examined IFN-α/β gene activation by different avian and human H5N1 isolates, if the IFN-α/β response restricts H5N1 growth and whether the different strains were equally capable to regulate the IFN-α/β system via their IFN-antagonistic NS1 proteins. Two human H5N1 isolates and a seasonal H3N2 strain propagated efficiently in human respiratory cells and induced little IFN-β, whereas three purely avian H5N1 strains were attenuated for replication and provoked higher IFN secretion. Replication of avian viruses was significantly enhanced on interferon-deficient cells, and exogenous IFN potently limited the growth of all strains in human cells. Moreover, IFN-α/β activation by all strains depended on retinoic acid-inducible gene I excluding principal differences in receptor activation between the different viruses. Interestingly, all H5N1 NS1 proteins suppressed IFN-α/β induction comparably well to the NS1 of seasonal IAV. Thus, our study shows that H5N1 strains are heterogeneous in their capacity to activate human cells in an NS1-independent manner. Our findings also suggest that H5N1 viruses need to acquire adaptive changes to circumvent strong IFN-α/β activation in human host cells. Since no single amino acid polymorphism could be associated with a respective high- or low induction phenotype we propose that the necessary adaptations to overcome the human IFN-α/β barrier involve mutations in multiple H5N1 genes.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Trends in respiratory virus circulation following COVID-19-targeted nonpharmaceutical interventions in Germany, January - September 2020

Djin-Ye Oh / Silke Buda / Barbara Biere / Janine Reiche / Frank Schlosser / Susanne Duwe / Marianne Wedde / Max von Kleist / Martin Mielke / Thorsten Wolff / Ralf Dürrwald

The Lancet Regional Health. Europe, Vol 6, Iss , Pp 100112- (2021)

Analysis of national surveillance data

2021

Abstract: Background: During the initial COVID-19 response, Germany's Federal Government implemented several nonpharmaceutical interventions (NPIs) that were instrumental in suppressing early exponential spread of SARS-CoV-2. NPI effect on the transmission of ... ...

Abstract	Background: During the initial COVID-19 response, Germany's Federal Government implemented several nonpharmaceutical interventions (NPIs) that were instrumental in suppressing early exponential spread of SARS-CoV-2. NPI effect on the transmission of other respiratory viruses has not been examined at the national level thus far. Methods: Upper respiratory tract specimens from 3580 patients with acute respiratory infection (ARI), collected within the nationwide German ARI Sentinel, underwent RT-PCR diagnostics for multiple respiratory viruses. The observation period (weeks 1-38 of 2020) included the time before, during and after a far-reaching contact ban. Detection rates for different viruses were compared to 2017-2019 sentinel data (15350 samples; week 1-38, 11823 samples). Findings: The March 2020 contact ban, which was followed by a mask mandate, was associated with an unprecedented and sustained decline of multiple respiratory viruses. Among these, rhinovirus was the single agent that resurged to levels equalling those of previous years. Rhinovirus rebound was first observed in children, after schools and daycares had reopened. By contrast, other nonenveloped viruses (i.e. gastroenteritis viruses reported at the national level) suppressed after the shutdown did not rebound. Interpretation: Contact restrictions with a subsequent mask mandate in spring may substantially reduce respiratory virus circulation. This reduction appears sustained for most viruses, indicating that the activity of influenza and other respiratory viruses during the subsequent winter season might be low,whereas rhinovirus resurgence, potentially driven by transmission in educational institutions in a setting of waning population immunity, might signal predominance of rhinovirus-related ARIs. Funding: Robert Koch-Institute and German Ministry of Health.
Keywords	Nonpharmaceutical interventions ; SARS-CoV-2 ; Respiratory virus ; Rhinovirus ; Surveillance ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Predominance of HA-222D/G polymorphism in influenza A(H1N1)pdm09 viruses associated with fatal and severe outcomes recently circulating in Germany.

Marianne Wedde / Stephanie Wählisch / Thorsten Wolff / Brunhilde Schweiger

PLoS ONE, Vol 8, Iss 2, p e

2013 Volume 57059

Abstract: Influenza A(H1N1)pdm09 viruses cause sporadically very severe disease including fatal clinical outcomes associated with pneumonia, viremia and myocarditis. A mutation characterized by the substitution of aspartic acid (wild-type) to glycine at position ... ...

Abstract	Influenza A(H1N1)pdm09 viruses cause sporadically very severe disease including fatal clinical outcomes associated with pneumonia, viremia and myocarditis. A mutation characterized by the substitution of aspartic acid (wild-type) to glycine at position 222 within the haemagglutinin gene (HA-D222G) was recorded during the 2009 H1N1 pandemic in Germany and other countries with significant frequency in fatal and severe cases. Additionally, A(H1N1)pdm09 viruses exhibiting the polymorphism HA-222D/G/N were detected both in the respiratory tract and in blood. Specimens from mild, fatal and severe cases were collected to study the heterogeneity of HA-222 in A(H1N1)pdm09 viruses circulating in Germany between 2009 and 2011. In order to enable rapid and large scale analysis we designed a pyrosequencing (PSQ) assay. In 2009/2010, the 222D wild-type of A(H1N1)pdm09 viruses predominated in fatal and severe outcomes. Moreover, co-circulating virus mutants exhibiting a D222G or D222E substitution (8/6%) as well as HA-222 quasispecies were identified (10%). Both the 222D/G and the 222D/G/N/V/Y polymorphisms were confirmed by TA cloning. PSQ analyses of viruses associated with mild outcomes revealed mainly the wild-type 222D and no D222G change in both seasons. However, an increase of variants with 222D/G polymorphism (60%) was characteristic for A(H1N1)pdm09 viruses causing fatal and severe cases in the season 2010/2011. Pure 222G viruses were not observed. Our results support the hypothesis that the D222G change may result from adaptation of viral receptor specificity to the lower respiratory tract. This could explain why transmission of the 222G variant is less frequent among humans. Thus, amino acid changes at HA position 222 may be the result of viral intra-host evolution leading to the generation of variants with an altered viral tropism.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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