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  1. Article ; Online: Phenotypic and Transcriptional Changes of Pulmonary Immune Responses in Dogs Following Canine Distemper Virus Infection

    Elisa Chludzinski / Johanna Klemens / Małgorzata Ciurkiewicz / Robert Geffers / Pauline Pöpperl / Melanie Stoff / Dai-Lun Shin / Georg Herrler / Andreas Beineke

    International Journal of Molecular Sciences, Vol 23, Iss 10019, p

    2022  Volume 10019

    Abstract: Canine distemper virus (CDV), a morbillivirus within the family Paramyxoviridae , is a highly contagious infectious agent causing a multisystemic, devastating disease in a broad range of host species, characterized by severe immunosuppression, ... ...

    Abstract Canine distemper virus (CDV), a morbillivirus within the family Paramyxoviridae , is a highly contagious infectious agent causing a multisystemic, devastating disease in a broad range of host species, characterized by severe immunosuppression, encephalitis and pneumonia. The present study aimed at investigating pulmonary immune responses of CDV-infected dogs in situ using immunohistochemistry and whole transcriptome analyses by bulk RNA sequencing. Spatiotemporal analysis of phenotypic changes revealed pulmonary immune responses primarily driven by MHC-II + , Iba-1 + and CD204 + innate immune cells during acute and subacute infection phases, which paralleled pathologic lesion development and coincided with high viral loads in CDV-infected lungs. CD20 + B cell numbers initially declined, followed by lymphoid repopulation in the advanced disease phase. Transcriptome analysis demonstrated an increased expression of transcripts related to innate immunity, antiviral defense mechanisms, type I interferon responses and regulation of cell death in the lung of CDV-infected dogs. Molecular analyses also revealed disturbed cytokine responses with a pro-inflammatory M1 macrophage polarization and impaired mucociliary defense in CDV-infected lungs. The exploratory study provides detailed data on CDV-related pulmonary immune responses, expanding the list of immunologic parameters potentially leading to viral elimination and virus-induced pulmonary immunopathology in canine distemper.
    Keywords apoptosis ; bulk RNA sequencing ; canine distemper ; cytokines ; immunohistochemistry ; innate immunity ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. 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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  3. Article ; Online: Ciliostasis of airway epithelial cells facilitates influenza A virus infection

    Yuguang Fu / Jie Tong / Fandan Meng / Doris Hoeltig / Guangliang Liu / Xiangping Yin / Georg Herrler

    Veterinary Research, Vol 49, Iss 1, Pp 1-

    2018  Volume 4

    Abstract: Abstract Porcine precision-cut lung slices (PCLS) were used to analyze the effect of the ciliary activity on infection of airway epithelial cells by influenza viruses. Treatment of slices with 2% NaCl for 30 min resulted in reversible ciliostasis. When ... ...

    Abstract Abstract Porcine precision-cut lung slices (PCLS) were used to analyze the effect of the ciliary activity on infection of airway epithelial cells by influenza viruses. Treatment of slices with 2% NaCl for 30 min resulted in reversible ciliostasis. When PCLS were infected by a swine influenza virus of the H3N2 subtype under ciliostatic conditions, the viral yield was about twofold or threefold higher at 24 or 48 h post-infection, respectively, as compared to slices with ciliary activity. Therefore, the cilia beating not only transports the mucus out of the airways, it also impedes virus infection.
    Keywords Veterinary medicine ; SF600-1100
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells.

    Markus Hoffmann / Nadine Krüger / Pawel Zmora / Florian Wrensch / Georg Herrler / Stefan Pöhlmann

    PLoS ONE, Vol 11, Iss 3, p e

    2016  Volume 0152134

    Abstract: New World bats have recently been discovered to harbor influenza A virus (FLUAV)-related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The internal proteins of batFLUAV are functional in mammalian cells. In contrast, no biological ... ...

    Abstract New World bats have recently been discovered to harbor influenza A virus (FLUAV)-related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The internal proteins of batFLUAV are functional in mammalian cells. In contrast, no biological functionality could be demonstrated for the surface proteins, hemagglutinin (HA)-like (HAL) and neuraminidase (NA)-like (NAL), and these proteins need to be replaced by their human counterparts to allow spread of batFLUAV in human cells. Here, we employed rhabdoviral vectors to study the role of HAL and NAL in viral entry. Vectors pseudotyped with batFLUAV-HAL and -NAL were able to enter bat cells but not cells from other mammalian species. Host cell entry was mediated by HAL and was dependent on prior proteolytic activation of HAL and endosomal low pH. In contrast, sialic acids were dispensable for HAL-driven entry. Finally, the type II transmembrane serine protease TMPRSS2 was able to activate HAL for cell entry indicating that batFLUAV can utilize human proteases for HAL activation. Collectively, these results identify viral and cellular factors governing host cell entry driven by batFLUAV surface proteins. They suggest that the absence of a functional receptor precludes entry of batFLUAV into human cells while other prerequisites for entry, HAL activation and protonation, are met in target cells of human origin.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Highly Pathogenic Avian Influenza A(H5N8) Virus in Gray Seals, Baltic Sea

    Dai-Lun Shin / Ursula Siebert / Jan Lakemeyer / Miguel Grilo / Iwona Pawliczka / Nai-Huei Wu / Peter Valentin-Weigand / Ludwig Haas / Georg Herrler

    Emerging Infectious Diseases, Vol 25, Iss 12, Pp 2295-

    2019  Volume 2298

    Abstract: We detected a highly pathogenic avian influenza A(H5N8) virus in lung samples of 2 gray seals (Halichoerus grypus) stranded on the Baltic coast of Poland in 2016 and 2017. This virus, clade 2.3.4.4 B, was closely related to avian H5N8 viruses circulating ...

    Abstract We detected a highly pathogenic avian influenza A(H5N8) virus in lung samples of 2 gray seals (Halichoerus grypus) stranded on the Baltic coast of Poland in 2016 and 2017. This virus, clade 2.3.4.4 B, was closely related to avian H5N8 viruses circulating in Europe at the time.
    Keywords H5N8 influenza virus ; highly pathogenic avian influenza ; marine mammals ; seal ; influenza ; viruses ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Centers for Disease Control and Prevention
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Sialic Acid Binding Properties of Soluble Coronavirus Spike (S1) Proteins

    Christine Winter / Georg Herrler / Ann-Kathrin Mork / Martina Hesse / Katarina Shahwan

    Viruses, Vol 5, Iss 8, Pp 1924-

    Differences between Infectious Bronchitis Virus and Transmissible Gastroenteritis Virus

    2013  Volume 1933

    Abstract: The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible ...

    Abstract The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible gastroenteritis virus (TGEV) and the spike protein of infectious bronchitis virus (IBV). Whereas sialic acid is the only receptor determinant known so far for IBV, TGEV requires interaction with its receptor aminopeptidase N to initiate infection of cells. Binding tests with soluble spike proteins carrying an IgG Fc-tag revealed pronounced differences between these two viral proteins. Binding of the IBV spike protein to host cells was in all experiments sialic acid dependent, whereas the soluble TGEV spike showed binding to APN but had no detectable sialic acid binding activity. Our results underline the different ways in which binding to sialoglycoconjugates is mediated by coronavirus spike proteins.
    Keywords Coronavirus ; spike protein ; sialic acid receptor ; TGEV ; IBV ; Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
    Language English
    Publishing date 2013-07-01T00:00:00Z
    Publisher Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Entry, Replication, Immune Evasion, and Neurotoxicity of Synthetically Engineered Bat-Borne Mumps Virus

    Nadine Krüger / Christian Sauder / Sarah Hüttl / Jan Papies / Kathleen Voigt / Georg Herrler / Kornelia Hardes / Torsten Steinmetzer / Claes Örvell / Jan Felix Drexler / Christian Drosten / Steven Rubin / Marcel Alexander Müller / Markus Hoffmann

    Cell Reports, Vol 25, Iss 2, Pp 312-320.e

    2018  Volume 7

    Abstract: Summary: Bats harbor a plethora of viruses with an unknown zoonotic potential. In-depth functional characterization of such viruses is often hampered by a lack of virus isolates. The genome of a virus closely related to human mumps viruses (hMuV) was ... ...

    Abstract Summary: Bats harbor a plethora of viruses with an unknown zoonotic potential. In-depth functional characterization of such viruses is often hampered by a lack of virus isolates. The genome of a virus closely related to human mumps viruses (hMuV) was detected in African fruit bats, batMuV. Efforts to characterize batMuV were based on directed expression of the batMuV glycoproteins or use of recombinant chimeric hMuVs harboring batMuV glycoprotein. Although these studies provided initial insights into the functionality of batMuV glycoproteins, the host range, replication competence, immunomodulatory functions, virulence, and zoonotic potential of batMuV remained elusive. Here, we report the successful rescue of recombinant batMuV. BatMuV infects human cells, is largely resistant to the host interferon response, blocks interferon induction and TNF-α activation, and is neurotoxic in rats. Anti-hMuV antibodies efficiently neutralize batMuV. The striking similarities between hMuV and batMuV point at the putative zoonotic potential of batMuV. : Humans were considered the only natural host of mumps viruses until the discovery of a closely related virus in bats. By reconstitution of the bat mumps virus, Krüger et al. show that the virus efficiently replicates in bat and in human cells, can evade innate immune responses in both hosts, and possesses neurotoxic properties. Keywords: mumps virus, bat-derived viruses, zoonosis, reverse genetics, viral entry, immune evasion
    Keywords Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Increased virulence of a PB2/HA mutant of an avian H9N2 influenza strain after three passages in porcine differentiated airway epithelial cells

    Yang, Wei / Darsaniya Punyadarsaniya / Fandan Meng / Georg Herrler / Jürgen Stech / Klaus Schughart / Nai-Huei Wu / Ruth L.O. Lambertz / Sarah R. Leist

    Veterinary microbiology. 2017 Nov., v. 211

    2017  

    Abstract: We analyzed the adaptation of influenza viruses to growth in differentiated airway epithelial cells of a new host by passaging an avian H9N2 virus three times in porcine precision-cut lung slices (PCLS). Sequence analysis revealed four mutations: one ... ...

    Abstract We analyzed the adaptation of influenza viruses to growth in differentiated airway epithelial cells of a new host by passaging an avian H9N2 virus three times in porcine precision-cut lung slices (PCLS). Sequence analysis revealed four mutations: one each in the PB2 and NS1 proteins, and two in the HA protein. In this study, we characterized the PB2 mutation G685R by generating recombinant H9N2 viruses containing the PB2 single mutation alone or in combination with one of the HA mutations (A190V or T212I). When analyzed in porcine cells − a tracheal cell line (NPTr) or PCLS − the PB2-685 mutant did not provide a growth advantage and had no effect on the ciliary activity which is a virulence marker of swine influenza viruses. Pathogenicity for mice was also not increased by the single PB2 mutation. However, both double mutants (HA-190+PB2-685 and HA-212+PB2-685) showed significantly increased virulence in mice. Therefore, the mutations in the HA and PB2 proteins may confer early adaptation of an avian H9N2 virus to a mammalian host. In conclusion, we expect that a broader ensemble of mutations will be required to render an H9N2 virus virulent for pigs.
    Keywords birds ; epithelial cells ; influenza ; Influenza A virus ; mice ; mutants ; mutation ; proteins ; sequence analysis ; swine ; virulence
    Language English
    Dates of publication 2017-11
    Size p. 129-134.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 753154-0
    ISSN 1873-2542 ; 0378-1135
    ISSN (online) 1873-2542
    ISSN 0378-1135
    DOI 10.1016/j.vetmic.2017.10.015
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Action mechanisms of lithium chloride on cell infection by transmissible gastroenteritis coronavirus.

    Xiaofeng Ren / Fandan Meng / Jiechao Yin / Guangxing Li / Xunliang Li / Chao Wang / Georg Herrler

    PLoS ONE, Vol 6, Iss 5, p e

    2011  Volume 18669

    Abstract: Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus. Lithium chloride (LiCl) has been found to be effective against several DNA viruses, such as Herpes simplex virus and vaccinia virus. Recently, we and others have reported the inhibitory ...

    Abstract Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus. Lithium chloride (LiCl) has been found to be effective against several DNA viruses, such as Herpes simplex virus and vaccinia virus. Recently, we and others have reported the inhibitory effect of LiCl on avian infectious bronchitis coronavirus (IBV) infection, an RNA virus. In the current study, the action mechanism of LiCl on cell infection by TGEV was investigated. Plaque assays and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenyl tetrazoliumbromide (MTT) assays showed that the cell infection by TGEV was inhibited in a dose-dependent manner, when LiCl was added to virus-infected cells; the cell infection was not affected when either cells or viruses were pretreated with the drug. The inhibition of TGEV infection in vitro by LiCl was observed at different virus doses and with different cell lines. The inhibitory effect of LiCl against TGEV infection and transcription was confirmed by RT-PCR and real-time PCR targeting viral S and 3CL-protease genes. The time-of-addition effect of the drug on TGEV infection indicated that LiCl acted on the initial and late stage of TGEV infection. The production of virus was not detected at 36 h post-infection due to the drug treatment. Moreover, immunofluorescence (IF) and flow cytometry analyses based on staining of Annexin V and propidium iodide staining of nuclei indicated that early and late cell apoptosis induced by TGEV was inhibited efficiently. The ability of LiCl to inhibit apoptosis was investigated by IF analysis of caspase-3 expression. Our data indicate that LiCl inhibits TGEV infection by exerting an anti-apoptotic effect. The inhibitory effect of LiCl was also observed with porcine epidemic diarrhea coronavirus. Together with other reports concerning the inhibitory effect of lithium salts on IBV in cell culture, our results indicate that LiCl may be a potent agent against porcine and avian coronaviruses.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Characterization of the sialic acid binding activity of influenza A viruses using soluble variants of the H7 and H9 hemagglutinins.

    Anne-Kathrin Sauer / Chi-Hui Liang / Jürgen Stech / Ben Peeters / Pascale Quéré / Christel Schwegmann-Wessels / Chung-Yi Wu / Chi-Huey Wong / Georg Herrler

    PLoS ONE, Vol 9, Iss 2, p e

    2014  Volume 89529

    Abstract: Binding of influenza viruses to target cells is mediated by the viral surface protein hemagglutinin. To determine the presence of binding sites for influenza A viruses on cells and tissues, soluble hemagglutinins of the H7 and H9 subtype were generated ... ...

    Abstract Binding of influenza viruses to target cells is mediated by the viral surface protein hemagglutinin. To determine the presence of binding sites for influenza A viruses on cells and tissues, soluble hemagglutinins of the H7 and H9 subtype were generated by connecting the hemagglutinin ectodomain to the Fc portion of human immunoglobulin G (H7Fc and H9Fc). Both chimeric proteins bound to different cells and tissues in a sialic acid-dependent manner. Pronounced differences were observed between H7Fc and H9Fc, in the binding both to different mammalian and avian cultured cells and to cryosections of the respiratory epithelium of different virus host species (turkey, chicken and pig). Binding of the soluble hemagglutinins was similar to the binding of virus particles, but showed differences in the binding pattern when compared to two sialic acid-specific plant lectins. These findings were substantiated by a comparative glycan array analysis revealing a very narrow recognition of sialoglycoconjugates by the plant lectins that does not reflect the glycan structures preferentially recognized by H7Fc and H9Fc. Thus, soluble hemagglutinins may serve as sialic acid-specific lectins and are a more reliable indicator of the presence of binding sites for influenza virus HA than the commonly used plant lectins.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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