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Article ; Online: A human protein that holds bird flu viruses at bay.

Graf, Laura / Staeheli, Peter

2023 Volume 619, Issue 7969, Page(s) 253–254

MeSH term(s)	Animals ; Humans ; Influenza in Birds/epidemiology ; Influenza A virus/genetics ; Birds ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control
Language	English
Publishing date	2023-05-31
Publishing country	England
Document type	News
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/d41586-023-01942-w
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Human MX2/MxB: a Potent Interferon-Induced Postentry Inhibitor of Herpesviruses and HIV-1.

Staeheli, Peter / Haller, Otto

Journal of virology

2018 Volume 92, Issue 24

Abstract: Interferons limit viral replication by inducing intracellular restriction factors, such as the GTPase MxB (also designated MX2), which inhibits HIV-1 and, as recently shown, herpesviruses. Inhibition of these viruses occurs at ill-defined steps after ... ...

Abstract	Interferons limit viral replication by inducing intracellular restriction factors, such as the GTPase MxB (also designated MX2), which inhibits HIV-1 and, as recently shown, herpesviruses. Inhibition of these viruses occurs at ill-defined steps after viral entry and requires formation of MxB dimers or oligomers, but GTP hydrolysis is needed only for blocking herpesviruses. Together with previous findings on related MxA, the new research on MxB highlights the mechanistic diversity by which MX proteins interfere with viral replication.
MeSH term(s)	HIV-1/drug effects ; HIV-1/physiology ; Herpesviridae/drug effects ; Herpesviridae/physiology ; Humans ; Interferons/pharmacology ; Models, Molecular ; Myxovirus Resistance Proteins/chemistry ; Myxovirus Resistance Proteins/metabolism ; Protein Conformation ; Protein Multimerization ; Up-Regulation ; Virus Internalization/drug effects ; Virus Replication/drug effects
Chemical Substances	MX2 protein, human ; Myxovirus Resistance Proteins ; Interferons (9008-11-1)
Language	English
Publishing date	2018-11-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00709-18
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Article ; Online: License to kill: IFN-λ regulates antifungal activity of neutrophils.

Schnepf, Daniel / Staeheli, Peter

Science immunology

2017 Volume 2, Issue 17

Abstract: Interferon-λ mediates antifungal immunity by stimulating neutrophils to generate reactive oxygen species. ...

Abstract	Interferon-λ mediates antifungal immunity by stimulating neutrophils to generate reactive oxygen species.
MeSH term(s)	Antifungal Agents ; Immunity, Innate ; Interferons ; Neutrophils
Chemical Substances	Antifungal Agents ; interferon type III ; Interferons (9008-11-1)
Language	English
Publishing date	2017-11-17
Publishing country	United States
Document type	Journal Article ; Comment
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.aap9614
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Article ; Online: Interferon-λ orchestrates innate and adaptive mucosal immune responses.

Ye, Liang / Schnepf, Daniel / Staeheli, Peter

Nature reviews. Immunology

2019 Volume 19, Issue 10, Page(s) 614–625

Abstract: Type III interferon (IFN-λ) was initially thought to have functions similar to those of the type I interferons (IFN-α and IFN-β). New findings have indicated, however, that IFN-λ has a non-redundant role in the innate antiviral, antifungal and ... ...

Abstract	Type III interferon (IFN-λ) was initially thought to have functions similar to those of the type I interferons (IFN-α and IFN-β). New findings have indicated, however, that IFN-λ has a non-redundant role in the innate antiviral, antifungal and antiprotozoal defences of mucosal barriers. In this Review, we highlight recent work showing that IFN-λ inhibits virus dissemination within the body and limits the transmission of respiratory and gastrointestinal viruses to naive hosts. We also discuss findings indicating that IFN-λ can act on neutrophils to prevent invasive pulmonary aspergillosis. We summarize results showing that IFN-λ signalling differs in several respects from IFN-α and IFN-β signalling, particularly in neutrophils. Finally, we discuss new findings indicating that IFN-λ is a potent enhancer of adaptive immune responses in the respiratory mucosa.
MeSH term(s)	Adaptive Immunity ; Animals ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Infections/immunology ; Interferon-gamma/physiology ; Intestinal Mucosa/immunology ; Neutrophils/immunology ; Respiratory System/immunology ; Signal Transduction/physiology
Chemical Substances	Interferon-gamma (82115-62-6)
Language	English
Publishing date	2019-06-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-019-0182-z
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Article ; Online: Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus.

Aschman, Tom / Schaffer, Sandra / Biniaris Georgallis, Stylianos Iason / Triantafyllopoulou, Antigoni / Staeheli, Peter / Voll, Reinhard E

International journal of molecular sciences

2021 Volume 22, Issue 21

Abstract: A pivotal role of type I interferons in systemic lupus erythematosus (SLE) is widely accepted. Type III interferons (IFN-λ) however, the most recently discovered cytokines grouped within the interferon family, have not been extensively studied in lupus ... ...

Abstract	A pivotal role of type I interferons in systemic lupus erythematosus (SLE) is widely accepted. Type III interferons (IFN-λ) however, the most recently discovered cytokines grouped within the interferon family, have not been extensively studied in lupus disease models yet. Growing evidence suggests a role for IFN-λ in regulating both innate and adaptive immune responses, and increased serum concentrations have been described in multiple autoimmune diseases including SLE. Using the pristane-induced lupus model, we found that mice with defective IFN-λ receptors (
MeSH term(s)	Animals ; Immunity, Cellular ; Immunity, Humoral ; Interferons/genetics ; Interferons/immunology ; Leukocytes/immunology ; Lupus Erythematosus, Systemic/chemically induced ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/immunology ; Mice ; Mice, Knockout ; Receptors, Interferon/deficiency ; Receptors, Interferon/immunology ; Terpenes/adverse effects ; Terpenes/pharmacology
Chemical Substances	IFNLR1 protein, mouse ; Receptors, Interferon ; Terpenes ; interferon type III ; pristane (26HZV48DT1) ; Interferons (9008-11-1)
Language	English
Publishing date	2021-10-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222111747
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Article ; Online: The Discovery of the Antiviral Resistance Gene Mx: A Story of Great Ideas, Great Failures, and Some Success.

Haller, Otto / Arnheiter, Heinz / Pavlovic, Jovan / Staeheli, Peter

Annual review of virology

2018 Volume 5, Issue 1, Page(s) 33–51

Abstract: The discovery of the Mx gene-dependent, innate resistance of mice against influenza virus was a matter of pure chance. Although the subsequent analysis of this antiviral resistance was guided by straightforward logic, it nevertheless led us into many ... ...

Abstract	The discovery of the Mx gene-dependent, innate resistance of mice against influenza virus was a matter of pure chance. Although the subsequent analysis of this antiviral resistance was guided by straightforward logic, it nevertheless led us into many blind alleys and was full of surprising turns and twists. Unexpectedly, this research resulted in the identification of one of the first interferon-stimulated genes and provided a new view of interferon action. It also showed that in many species, MX proteins have activities against a broad range of viruses. To this day, Mx research continues to flourish and to provide insights into the never-ending battle between viruses and their hosts.
MeSH term(s)	Animals ; Biomedical Research/history ; Disease Resistance ; History, 20th Century ; History, 21st Century ; Humans ; Immunity, Innate ; Interferons/metabolism ; Myxovirus Resistance Proteins/metabolism ; Viruses/immunology
Chemical Substances	Myxovirus Resistance Proteins ; Interferons (9008-11-1)
Language	English
Publishing date	2018-06-29
Publishing country	United States
Document type	Historical Article ; Journal Article ; Review
ZDB-ID	2764224-0
ISSN	2327-0578 ; 2327-056X
ISSN (online)	2327-0578
ISSN	2327-056X
DOI	10.1146/annurev-virology-092917-043525
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Article: IFN-λ is protective against lethal oral

Murillo-León, Mateo / Bastidas-Quintero, Aura M / Endres, Niklas S / Schnepf, Daniel / Delgado-Betancourt, Estefanía / Ohnemus, Annette / Taylor, Gregory A / Schwemmle, Martin / Staeheli, Peter / Steinfeldt, Tobias

bioRxiv : the preprint server for biology

2023

Abstract: Interferons are essential for innate and adaptive immune responses against a wide variety of pathogens. Interferon lambda (IFN-λ) protects mucosal barriers during pathogen exposure. The intestinal epithelium is the first contact site ... ...

Abstract	Interferons are essential for innate and adaptive immune responses against a wide variety of pathogens. Interferon lambda (IFN-λ) protects mucosal barriers during pathogen exposure. The intestinal epithelium is the first contact site for
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.24.529861
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Article ; Online: mRNA 3'UTR lengthening by alternative polyadenylation attenuates inflammatory responses and correlates with virulence of Influenza A virus.

Bergant, Valter / Schnepf, Daniel / de Andrade Krätzig, Niklas / Hubel, Philipp / Urban, Christian / Engleitner, Thomas / Dijkman, Ronald / Ryffel, Bernhard / Steiger, Katja / Knolle, Percy A / Kochs, Georg / Rad, Roland / Staeheli, Peter / Pichlmair, Andreas

Nature communications

2023 Volume 14, Issue 1, Page(s) 4906

Abstract: Changes of mRNA 3'UTRs by alternative polyadenylation (APA) have been associated to numerous pathologies, but the mechanisms and consequences often remain enigmatic. By combining transcriptomics, proteomics and recombinant viruses we show that all tested ...

Abstract	Changes of mRNA 3'UTRs by alternative polyadenylation (APA) have been associated to numerous pathologies, but the mechanisms and consequences often remain enigmatic. By combining transcriptomics, proteomics and recombinant viruses we show that all tested strains of IAV, including A/PR/8/34(H1N1) (PR8) and A/Cal/07/2009 (H1N1) (Cal09), cause APA. We mapped the effect to the highly conserved glycine residue at position 184 (G184) of the viral non-structural protein 1 (NS1). Unbiased mass spectrometry-based analyses indicate that NS1 causes APA by perturbing the function of CPSF4 and that this function is unrelated to virus-induced transcriptional shutoff. Accordingly, IAV strain PR8, expressing an NS1 variant with weak CPSF binding, does not induce host shutoff but only APA. However, recombinant IAV (PR8) expressing NS1(G184R) lacks binding to CPSF4 and thereby also the ability to cause APA. Functionally, the impaired ability to induce APA leads to an increased inflammatory cytokine production and an attenuated phenotype in a mouse infection model. Investigating diverse viral infection models showed that APA induction is a frequent ability of many pathogens. Collectively, we propose that targeting of the CPSF complex, leading to widespread alternative polyadenylation of host transcripts, constitutes a general immunevasion mechanism employed by a variety of pathogenic viruses.
MeSH term(s)	Animals ; Mice ; Influenza A virus/genetics ; 3' Untranslated Regions/genetics ; Influenza A Virus, H1N1 Subtype/metabolism ; Polyadenylation ; Virulence/genetics ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism
Chemical Substances	3' Untranslated Regions ; Viral Nonstructural Proteins
Language	English
Publishing date	2023-08-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-40469-6
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Article ; Online: Passively transferred M2e-specific monoclonal antibody reduces influenza A virus transmission in mice.

Kolpe, Annasaheb / Schepens, Bert / Ye, Liang / Staeheli, Peter / Saelens, Xavier

Antiviral research

2018 Volume 158, Page(s) 244–254

Abstract: Influenza represents a global public health threat. Currently available influenza vaccines are effective against strain-matched influenza A and B viruses but do not protect against novel pandemic viruses. Vaccine candidates that target conserved B or T ... ...

Abstract	Influenza represents a global public health threat. Currently available influenza vaccines are effective against strain-matched influenza A and B viruses but do not protect against novel pandemic viruses. Vaccine candidates that target conserved B or T cell epitopes of influenza viruses could circumvent this shortcoming. The conserved extracellular domain of matrix protein 2 (M2e) of influenza A is an example of such a broadly protective vaccine candidate. Protection by M2e-based vaccine candidates largely depends on M2e-specific IgG antibodies. Here we show that the M2e-specific IgG2a monoclonal antibody 65 (MAb 65) can reduce influenza A/Udorn/72 (H3N2) and A/Hong Kong/68 (H3N2) virus plaque formation. This effect was not observed with other influenza A virus strains tested. We further show that passive transfer of MAb 65 to mice can reduce viral loads in the upper and lower airways, which results in reduced transmission of A/Udorn/72 and A/Hong Kong/68 viruses to cohoused, unimmunized contact mice. Virus restriction by passively transferred Mab 65 was significantly less pronounced in Fcgr1
MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Disease Models, Animal ; Dogs ; Female ; Immunization ; Immunization, Passive ; Immunoglobulin G ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza A virus/immunology ; Influenza Vaccines/immunology ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Inbred BALB C ; Mice, Inbred DBA ; Mice, Knockout ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/prevention & control ; Orthomyxoviridae Infections/transmission ; Receptors, IgG/genetics ; Viral Matrix Proteins/immunology
Chemical Substances	Antibodies, Monoclonal ; Fcgr3 protein, mouse ; Immunoglobulin G ; Influenza Vaccines ; M1 protein, Influenza A virus ; Receptors, IgG ; Viral Matrix Proteins
Language	English
Publishing date	2018-09-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2018.08.017
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Article ; Online: Interferon-λ Improves the Efficacy of Intranasally or Rectally Administered Influenza Subunit Vaccines by a Thymic Stromal Lymphopoietin-Dependent Mechanism.

Ye, Liang / Schnepf, Daniel / Ohnemus, Annette / Ong, Li Ching / Gad, Hans Henrik / Hartmann, Rune / Lycke, Nils / Staeheli, Peter

Frontiers in immunology

2021 Volume 12, Page(s) 749325

Abstract: Previous work showed that interferon-λ (IFN-λ) can trigger the synthesis of thymic stromal lymphopoietin (TSLP) by specialized epithelial cells in the upper airways of mice, thereby improving the performance of intranasally administered influenza ... ...

Abstract	Previous work showed that interferon-λ (IFN-λ) can trigger the synthesis of thymic stromal lymphopoietin (TSLP) by specialized epithelial cells in the upper airways of mice, thereby improving the performance of intranasally administered influenza vaccines. Here we demonstrate that protein-only influenza vaccines containing either IFN-λ or TSLP boosted antigen-specific IgG1 and IgA responses and enhanced the resistance of mice to influenza virus challenge, irrespective of whether the vaccines were applied
MeSH term(s)	Administration, Intranasal ; Administration, Rectal ; Animals ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Bronchoalveolar Lavage Fluid/immunology ; Cytokines/administration & dosage ; Female ; Immunoglobulin A/immunology ; Immunoglobulin G/immunology ; Immunoglobulins/genetics ; Influenza A virus ; Influenza Vaccines/administration & dosage ; Interferons/administration & dosage ; Lymph Nodes/cytology ; Lymph Nodes/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; Orthomyxoviridae Infections/prevention & control ; Receptors, Cytokine/genetics ; Vaccines, Subunit/administration & dosage ; Thymic Stromal Lymphopoietin ; Mice
Chemical Substances	Antibodies, Viral ; Cytokines ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulins ; Influenza Vaccines ; Receptors, Cytokine ; Tslpr protein, mouse ; Vaccines, Subunit ; Interferons (9008-11-1) ; Thymic Stromal Lymphopoietin (GT0IL38SP4)
Language	English
Publishing date	2021-09-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.749325
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