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Article ; Online: Reduced IFN-ß inhibitory activity of Lagos bat virus phosphoproteins in human compared to Eidolon helvum bat cells.

Jan Papies / Andrea Sieberg / Daniel Ritz / Daniela Niemeyer / Christian Drosten / Marcel A Müller

PLoS ONE, Vol 17, Iss 3, p e

2022 Volume 0264450

Abstract: Eidolon helvum bats are reservoir hosts for highly pathogenic lyssaviruses often showing limited disease upon natural infection. An enhanced antiviral interferon (IFN) response combined with reduced inflammation might be linked to the apparent virus ... ...

Abstract	Eidolon helvum bats are reservoir hosts for highly pathogenic lyssaviruses often showing limited disease upon natural infection. An enhanced antiviral interferon (IFN) response combined with reduced inflammation might be linked to the apparent virus tolerance in bats. Lyssavirus phosphoproteins inhibit the IFN response with virus strain-specific efficiency. To date, little is known regarding the lyssavirus P-dependent anti-IFN countermeasures in bats, mainly due to a lack of in vitro tools. By using E. helvum bat cell cultures in a newly established bat-specific IFN-promoter activation assay, we analyzed the IFN-ß inhibitory activity of multiple lyssavirus P in E. helvum compared to human cells. Initial virus infection studies with a recently isolated E. helvum-borne Lagos bat virus street strain from Ghana showed enhanced LBV propagation in an E. helvum lung cell line compared to human A549 lung cells at later time points suggesting effective viral countermeasures against cellular defense mechanisms. A direct comparison of the IFN-ß inhibitory activity of the LBV-GH P protein with other lyssavirus P proteins showed that LBV-GH P and RVP both strongly inhibited the bat IFN-β promotor activation (range 75-90%) in EidLu/20.2 and an E. helvum kidney cell line. Conversely, LBV-GH P blocked the activation of the human IFN-β promoter less efficiently compared to a prototypic Rabies virus P protein (range LBV P 52-68% vs RVP 71-95%) in two different human cell lines (HEK-293T, A549). The same pattern was seen for two prototypic LBV P variants suggesting an overall reduced LBV P IFN-ß inhibitory activity in human cells as compared to E. helvum bat cells. Increased IFN-ß inhibition by lyssavirus P in reservoir host cells might be a result of host-specific adaptation processes towards an enhanced IFN response in bat cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
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: Reduced IFN-ß inhibitory activity of Lagos bat virus phosphoproteins in human compared to Eidolon helvum bat cells

Jan Papies / Andrea Sieberg / Daniel Ritz / Daniela Niemeyer / Christian Drosten / Marcel A. Müller

PLoS ONE, Vol 17, Iss

2022 Volume 3

Abstract	Eidolon helvum bats are reservoir hosts for highly pathogenic lyssaviruses often showing limited disease upon natural infection. An enhanced antiviral interferon (IFN) response combined with reduced inflammation might be linked to the apparent virus tolerance in bats. Lyssavirus phosphoproteins inhibit the IFN response with virus strain-specific efficiency. To date, little is known regarding the lyssavirus P-dependent anti-IFN countermeasures in bats, mainly due to a lack of in vitro tools. By using E. helvum bat cell cultures in a newly established bat-specific IFN-promoter activation assay, we analyzed the IFN-ß inhibitory activity of multiple lyssavirus P in E. helvum compared to human cells. Initial virus infection studies with a recently isolated E. helvum-borne Lagos bat virus street strain from Ghana showed enhanced LBV propagation in an E. helvum lung cell line compared to human A549 lung cells at later time points suggesting effective viral countermeasures against cellular defense mechanisms. A direct comparison of the IFN-ß inhibitory activity of the LBV-GH P protein with other lyssavirus P proteins showed that LBV-GH P and RVP both strongly inhibited the bat IFN-β promotor activation (range 75–90%) in EidLu/20.2 and an E. helvum kidney cell line. Conversely, LBV-GH P blocked the activation of the human IFN-β promoter less efficiently compared to a prototypic Rabies virus P protein (range LBV P 52–68% vs RVP 71–95%) in two different human cell lines (HEK-293T, A549). The same pattern was seen for two prototypic LBV P variants suggesting an overall reduced LBV P IFN-ß inhibitory activity in human cells as compared to E. helvum bat cells. Increased IFN-ß inhibition by lyssavirus P in reservoir host cells might be a result of host-specific adaptation processes towards an enhanced IFN response in bat cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
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: Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2

Qinya Xie / Caterina Prelli Bozzo / Laura Eiben / Sabrina Noettger / Dorota Kmiec / Rayhane Nchioua / Daniela Niemeyer / Meta Volcic / Jung-Hyun Lee / Fabian Zech / Konstantin M.J. Sparrer / Christian Drosten / Frank Kirchhoff

iScience, Vol 26, Iss 4, Pp 106395- (2023)

2023

Abstract: Summary: Opposing effects of interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains ... ...

Abstract	Summary: Opposing effects of interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains poorly understood. Here, we demonstrate that endogenous expression of IFITM2 and/or IFITM3 is critical for efficient replication of SARS-CoV-1, SARS-CoV-2 and hCoV-OC43 but has little effect on MERS-, NL63-and 229E-hCoVs. In contrast, overexpression of IFITMs inhibits all these hCoVs, and the corresponding spike-containing pseudo-particles, except OC43, which is enhanced by IFITM3. We further demonstrate that overexpression of IFITMs impairs cell surface expression of ACE2 representing the entry receptor of SARS-CoVs and hCoV-NL63 but not hCoV-OC43. Our results explain the inhibitory effects of artificial IFITM overexpression on ACE2-tropic SARS-CoVs and show that three hCoVs, including major causative agents of severe respiratory disease, hijack IFITMs for efficient infection of human cells.
Keywords	Protein ; Immunity ; Virology ; Science ; Q
Subject code	570
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pathogens associated with hospitalization due to acute lower respiratory tract infections in children in rural Ghana

Ralf Krumkamp / Matin Kohsar / Kolja Nolte / Benedikt Hogan / Daniel Eibach / Anna Jaeger / Charity Wiafe Akenten / Christian Drosten / Kennedy Gyau Boahen / Nimako Sarpong / Isabella Eckerle / Tabea Binger / Ellis Owusu-Dabo / Jürgen May / Benno Kreuels

Scientific Reports, Vol 13, Iss 1, Pp 1-

a case–control study

2023 Volume 9

Abstract: Abstract Respiratory infections are one of the most common causes of death among children under the age of five years. Data on prevalence and relevance of specific organisms in African children are still lacking. This case–control-study investigated ... ...

Abstract	Abstract Respiratory infections are one of the most common causes of death among children under the age of five years. Data on prevalence and relevance of specific organisms in African children are still lacking. This case–control-study investigated prevalence and relevance of specific organisms in Ghanaian children admitted to hospital with symptoms of lower respiratory tract infection (LRTI). Pharyngeal swabs were taken and tested by PCR for 19 respiratory isolates. Adjusted odds ratios (aORs) were calculated to estimate associations between isolates and admission with LRTI. Population attributable fractions (PAFs) were calculated to assess the proportion of LRTI cases due to a particular pathogen. The study included 327 cases and 562 controls. We found associations between detection and admission for LRTI for influenza (aOR 98.6; 95% confidence interval (CI) 20.0–1789.6), respiratory syncytial virus (aOR 40.2; 95% CI 7.2–758.6), H. influenzae (aOR 4.1; 95% CI 2.2–7.9) and S. pneumoniae (aOR 2.4; 95% CI 1.7–3.4). PAFs ≥ 10% were observed for S. pneumoniae (30%; 95% CI 26–42), H. influenzae (10%; 95% CI 2–19) and influenza (10%; 95% CI 2–18). This study highlights the need for heightened surveillance and development of effective vaccines for respiratory pathogens other than SARS-CoV-2 in the future.
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses

Anna-Lena Sander / Andres Moreira-Soto / Stoian Yordanov / Ivan Toplak / Andrea Balboni / Ramón Seage Ameneiros / Victor Corman / Christian Drosten / Jan Felix Drexler

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

2022 Volume 8

Abstract: Genomic analyses of spike glycoprotein genes of European bat SARS-related coronaviruses suggest that furin cleavage sites can be acquired in the bat reservoir via conserved molecular mechanisms, supporting a natural origin of SARS-CoV-2. ...

Abstract	Genomic analyses of spike glycoprotein genes of European bat SARS-related coronaviruses suggest that furin cleavage sites can be acquired in the bat reservoir via conserved molecular mechanisms, supporting a natural origin of SARS-CoV-2.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Stability and neutralising capacity of SARS-CoV-2-specific antibodies in convalescent plasma

Torsten Tonn / Victor M Corman / Matthias Johnsen / Anja Richter / Roman N Rodionov / Christian Drosten / Stefan R Bornstein

The Lancet Microbe, Vol 1, Iss 2, Pp e63- (2020)

2020

Keywords	Medicine (General) ; R5-920 ; Microbiology ; QR1-502
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pharmacological inhibition of bromodomain and extra-terminal proteins induces an NRF-2-mediated antiviral state that is subverted by SARS-CoV-2 infection.

PLoS Pathogens, Vol 19, Iss 9, p e

2023 Volume 1011657

Abstract: Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential prophylactics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-mediated antiviral activity and its susceptibility ... ...

Abstract	Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential prophylactics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-mediated antiviral activity and its susceptibility to viral subversion remain incompletely understood. Pretreatment of cells with iBETs inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. The antiviral activity manifested itself by reduced reporter expression of recombinant viruses, and reduced viral RNA quantities and infectious titers in the culture supernatant. While we confirmed JQ-1-mediated downregulation of expression of angiotensin-converting enzyme 2 (ACE2) and interferon-stimulated genes (ISGs), multi-omics analysis addressing the chromatin accessibility, transcriptome and proteome uncovered induction of an antiviral nuclear factor erythroid 2-related factor 2 (NRF-2)-mediated cytoprotective response as an additional mechanism through which JQ-1 inhibits SARS-CoV-2 replication. Pharmacological inhibition of NRF-2, and knockdown of NRF-2 and its target genes reduced JQ-1-mediated inhibition of SARS-CoV-2 replication. Serial passaging of SARS-CoV-2 in the presence of JQ-1 resulted in predominance of ORF6-deficient variant, which exhibited resistance to JQ-1 and increased sensitivity to exogenously administered type I interferon (IFN-I), suggesting a minimised need for SARS-CoV-2 ORF6-mediated repression of IFN signalling in the presence of JQ-1. Importantly, JQ-1 exhibited a transient antiviral activity when administered prophylactically in human airway bronchial epithelial cells (hBAECs), which was gradually subverted by SARS-CoV-2, and no antiviral activity when administered therapeutically following an established infection. We propose that JQ-1 exerts pleiotropic effects that collectively induce an antiviral state in the host, which is ultimately nullified by SARS-CoV-2 infection, raising questions about the clinical suitability of the iBETs in the context of COVID-19.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-09-01T00:00:00Z
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: Virus- and Interferon Alpha-Induced Transcriptomes of Cells from the Microbat Myotis daubentonii

Martin Hölzer / Andreas Schoen / Julia Wulle / Marcel A. Müller / Christian Drosten / Manja Marz / Friedemann Weber

iScience, Vol 19, Iss , Pp 647-

2019 Volume 661

Abstract: Summary: Antiviral interferons (IFN-alpha/beta) are possibly responsible for the high tolerance of bats to zoonotic viruses. Previous studies focused on the IFN system of megabats (suborder Yinpterochiroptera). We present statistically robust RNA ... ...

Abstract	Summary: Antiviral interferons (IFN-alpha/beta) are possibly responsible for the high tolerance of bats to zoonotic viruses. Previous studies focused on the IFN system of megabats (suborder Yinpterochiroptera). We present statistically robust RNA sequencing (RNA-seq) data on transcriptomes of cells from the “microbat” Myotis daubentonii (suborder Yangochiroptera) responding at 6 and 24 h to either an IFN-inducing virus or treatment with IFN. Our data reveal genes triggered only by virus, either in both humans and Myotis (CCL4, IFNL3, CH25H), or exclusively in Myotis (STEAP4). Myotis cells also express a series of conserved IFN-stimulated genes (ISGs) and an unusually high paralog number of the antiviral ISG BST2 (tetherin) but lack several ISGs that were described for megabats (EMC2, FILIP1, IL17RC, OTOGL, SLC24A1). Also, in contrast to megabats, we detected neither different IFN-alpha subtypes nor an unusually high baseline expression of IFNs. Thus, Yangochiroptera microbats, represented by Myotis, may possess an IFN system with distinctive features. : Biological Sciences; Immunity; Omics; Transcriptomics Subject Areas: Biological Sciences, Immunity, Omics, Transcriptomics
Keywords	Science ; Q
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Adenovirus infection is associated with altered gut microbial communities in a non-human primate

Wasimuddin / Victor M. Corman / Jörg U. Ganzhorn / Jacques Rakotondranary / Yedidya R. Ratovonamana / Christian Drosten / Simone Sommer

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 12

Abstract: Abstract Adenovirus (AdV) infections are one of the main causes of diarrhea in young children. Enteric AdVs probably disrupt gut microbial defences, which can result in diarrhea. To understand the role of the gut microbiome in AdV-induced pathologies, we ...

Abstract	Abstract Adenovirus (AdV) infections are one of the main causes of diarrhea in young children. Enteric AdVs probably disrupt gut microbial defences, which can result in diarrhea. To understand the role of the gut microbiome in AdV-induced pathologies, we investigated the gut microbiome of a naturally AdV-infected non-human primate species, the Malagasy mouse lemur (Microcebus griseorufus), which represents an important model in understanding the evolution of diseases. We observed that AdV infection is associated with disruption of the gut microbial community composition. In AdV+ lemurs, several commensal taxa essential for a healthy gut microbiome decreased, whereas genera containing potential pathogens, such as Neisseria, increased in abundance. Microbial co-occurrence networks revealed a loss of important microbial community interactions in AdV+ lemurs and an overrepresentation of Prevotellaceae. The observation of enteric virus-associated loss of commensal bacteria and associated shifts towards pathobionts may represent the missing link for a better understanding of AdV-induced effects in humans, and also for their potential as drivers of co-infections, an area of research that has been largely neglected so far.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evidence of MHC class I and II influencing viral and helminth infection via the microbiome in a non-human primate.

B Karina Montero / Wasimuddin / Nina Schwensow / Mark A F Gillingham / Yedidya R Ratovonamana / S Jacques Rakotondranary / Victor Corman / Christian Drosten / Jörg U Ganzhorn / Simone Sommer

PLoS Pathogens, Vol 17, Iss 11, p e

2021 Volume 1009675

Abstract: Until recently, the study of major histocompability complex (MHC) mediated immunity has focused on the direct link between MHC diversity and susceptibility to parasite infection. However, MHC genes can also influence host health indirectly through the ... ...

Abstract	Until recently, the study of major histocompability complex (MHC) mediated immunity has focused on the direct link between MHC diversity and susceptibility to parasite infection. However, MHC genes can also influence host health indirectly through the sculpting of the bacterial community that in turn shape immune responses. We investigated the links between MHC class I and II gene diversity gut microbiome diversity and micro- (adenovirus, AdV) and macro- (helminth) parasite infection probabilities in a wild population of non-human primates, mouse lemurs of Madagascar. This setup encompasses a plethora of underlying interactions between parasites, microbes and adaptive immunity in natural populations. Both MHC classes explained shifts in microbiome composition and the effect was driven by a few select microbial taxa. Among them were three taxa (Odoribacter, Campylobacter and Prevotellaceae-UCG-001) which were in turn linked to AdV and helminth infection status, correlative evidence of the indirect effect of the MHC via the microbiome. Our study provides support for the coupled role of MHC diversity and microbial flora as contributing factors of parasite infection.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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