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Article ; Online: To Conquer the Host, Influenza Virus Is Packing It In: Interferon-Antagonistic Strategies beyond NS1.

Weber-Gerlach, Michaela / Weber, Friedemann

2016 Volume 90, Issue 19, Page(s) 8389–8394

Abstract: The nonstructural protein NS1 is well established as a virulence factor of influenza A virus counteracting induction of the antiviral type I interferon system. Recent studies now show that viral structural proteins, their derivatives, and even the genome ...

Abstract	The nonstructural protein NS1 is well established as a virulence factor of influenza A virus counteracting induction of the antiviral type I interferon system. Recent studies now show that viral structural proteins, their derivatives, and even the genome itself also contribute to keeping the host defense under control. Here, we summarize the current knowledge on these NS1-independent interferon escape strategies.
MeSH term(s)	Host-Pathogen Interactions ; Immune Evasion ; Interferons/antagonists & inhibitors ; Orthomyxoviridae/immunology ; Orthomyxoviridae/physiology ; Viral Nonstructural Proteins/metabolism ; Viral Structural Proteins/metabolism
Chemical Substances	INS1 protein, influenza virus ; Viral Nonstructural Proteins ; Viral Structural Proteins ; Interferons (9008-11-1)
Language	English
Publishing date	2016-10-01
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.00041-16
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Article ; Online: Standing on three legs: antiviral activities of RIG-I against influenza viruses.

Weber-Gerlach, Michaela / Weber, Friedemann

Current opinion in immunology

2016 Volume 42, Page(s) 71–75

Abstract: Influenza A virus (FLUAV) is a severe pathogen of humans, able to unleash epidemics and pandemics of respiratory disease. For the host to survive virus infection, it is essential to rapidly recognize the pathogen and induce the synthesis of antiviral ... ...

Abstract	Influenza A virus (FLUAV) is a severe pathogen of humans, able to unleash epidemics and pandemics of respiratory disease. For the host to survive virus infection, it is essential to rapidly recognize the pathogen and induce the synthesis of antiviral type I interferons (IFNs). The IFN system provides a broad spectrum of sensors that respond to conserved, virus-associated molecular patterns. For FLUAV, the RNA helicase RIG-I represents the major innate immune sensor, mainly binding and reacting to the 5' triphosphate dsRNA 'panhandle' that is formed by the conserved 5' and 3' end sequences of the viral ssRNA genome. Besides the well-known function of RIG-I in the signaling chain that leads to IFN induction, recent data suggests that RIG-I performs also other antiviral activities. In this review, we summarize the current knowledge on RIG-I-mediated recognition of FLUAV, and how RIG-I interferes with virus replication. We will highlight three major functions of RIG-I against FLUAV: IFN induction, signaling-independent direct antiviral activity, and assembly of an inflammasome.
MeSH term(s)	Animals ; Humans ; Immunity, Innate ; Inflammasomes/metabolism ; Influenza A virus/physiology ; Influenza, Human/immunology ; Interferon Type I/genetics ; Interferon Type I/metabolism ; Mice ; Orthomyxoviridae Infections/immunology ; Pathogen-Associated Molecular Pattern Molecules/immunology ; RNA, Viral/immunology ; Receptors, Pattern Recognition/metabolism ; Receptors, Retinoic Acid/metabolism ; Signal Transduction ; Virus Replication
Chemical Substances	Inflammasomes ; Interferon Type I ; PLAAT4 protein, human ; Pathogen-Associated Molecular Pattern Molecules ; RNA, Viral ; Receptors, Pattern Recognition ; Receptors, Retinoic Acid
Language	English
Publishing date	2016-06-16
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2016.05.016
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Article ; Online: The secRNome of Listeria monocytogenes Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon.

Frantz, Renate / Teubner, Lisa / Schultze, Tilman / La Pietra, Luigi / Müller, Christin / Gwozdzinski, Konrad / Pillich, Helena / Hain, Torsten / Weber-Gerlach, Michaela / Panagiotidis, Georgios-Dimitrios / Mostafa, Ahmed / Weber, Friedemann / Rohde, Manfred / Pleschka, Stephan / Chakraborty, Trinad / Abu Mraheil, Mobarak

mBio

2019 Volume 10, Issue 5

Abstract: Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular ... ...

Abstract	Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular pathogen
MeSH term(s)	Animals ; Cells, Cultured ; Gene Deletion ; Immunologic Factors/metabolism ; Interferon-beta/metabolism ; Listeria monocytogenes/genetics ; Listeria monocytogenes/immunology ; Listeria monocytogenes/metabolism ; Macrophages/microbiology ; Mice, Inbred C57BL ; RNA, Bacterial/genetics ; RNA, Bacterial/immunology ; RNA, Bacterial/metabolism ; RNA, Small Untranslated/genetics ; RNA, Small Untranslated/immunology ; RNA, Small Untranslated/metabolism
Chemical Substances	Immunologic Factors ; RNA, Bacterial ; RNA, Small Untranslated ; Interferon-beta (77238-31-4)
Language	English
Publishing date	2019-10-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.01223-19
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The secRNome of Listeria monocytogenes Harbors Small Noncoding RNAs That Are Potent Inducers of Beta Interferon.

mBio

2019

Abstract: Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular pathogen Listeria monocytogenes induces high levels of type I interferons (alpha/beta interferons [IFN-α/β]) to create a growth- ...

Abstract	Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular pathogen Listeria monocytogenes induces high levels of type I interferons (alpha/beta interferons [IFN-α/β]) to create a growth-permissive microenvironment during infection. We previously demonstrated that RNAs secreted by L. monocytogenes (comprising the secRNome) are potent inducers of IFN-β. We determined the composition and diversity of the members of the secRNome and found that they are uniquely enriched for noncoding small RNAs (sRNAs). Testing of individual sRNAs for their ability to induce IFN revealed several sRNAs with this property. We examined ril32, an intracellularly expressed sRNA that is highly conserved for the species L. monocytogenes and that was the most potent inducer of IFN-β expression of all the sRNAs tested in this study, in more detail. The rli32-induced IFN-β response is RIG-I (retinoic acid inducible gene I) dependent, and cells primed with rli32 inhibit influenza virus replication. We determined the rli32 motif required for IFN induction. rli32 overproduction promotes intracellular bacterial growth, and a mutant lacking rli32 is restricted for intracellular growth in macrophages. rli32-overproducing bacteria are resistant to H2O2 and exhibit both increased catalase activity and changes in the cell envelope. Comparative transcriptome sequencing (RNA-Seq) analysis indicated that ril32 regulates expression of the lhrC locus, previously shown to be involved in cell envelope stress. Inhibition of IFN-β signaling by ruxolitinib reduced rli32-dependent intracellular bacterial growth, indicating a link between induction of the interferon system and bacterial physiology. rli32 is, to the best of our knowledge, the first secreted individual bacterial sRNA known to trigger the induction of the type I IFN response.IMPORTANCE Interferons are potent and broadly acting cytokines that stimulate cellular responses to nucleic acids of unusual structures or locations. While protective when induced following viral infections, the induction of interferons is detrimental to the host during L. monocytogenes infection. Here, we identify specific sRNAs, secreted by the bacterium, with the capacity to induce type I IFN. Further analysis of the most potent sRNA, rli32, links the ability to induce RIG-I-dependent induction of the type I IFN response to the intracellular growth properties of the bacterium. Our findings emphasize the significance of released RNA for Listeria infection and shed light on a compartmental strategy used by an intracellular pathogen to modulate host responses to its advantage.
Keywords	Listeria monocytogenes ; secreted RNA ; type I IFN
Subject code	572
Language	English
Publishing date	2019-10-08
Publisher	ASM
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online ; Thesis: Virus-host interplay-Immediate virus recognition by RIG-I and PKR and viral counterstrategies

Gerlach, Michaela [Verfasser] / Weber, Friedemann [Akademischer Betreuer]

2015

Author's details	Michaela Gerlach. Betreuer: Friedemann Weber
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	English
Publisher	Philipps-Universität Marburg
Publishing place	Marburg
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Large-Scale SARS-CoV-2 Testing Utilizing Saliva and Transposition Sample Pooling.

Patterson, Joseph R / Cole-Strauss, Allyson / Kuhn, Nathan / Mercier, Carlene / Kochmanski, Joseph / Gerlach, John A / LeVeque, Rhiannon M / Neugebauer, Kerri A / Conner, Kayla N / Gomez, Jasper / Hennes, Mark G / Thompson, Kaje'ne E / Rytlewski, Destinee L / Bigwood, Chloe C / Scharmen, Amy / Simjanovski, Gabriel / Riley, Cassidy / Donaldson, Jessica / Yasin, Dilann /

Kouja, Najwa / Contejean, Zaria / Burnett, Michaela / Aminova, Shakhlo / Yawson, Nat Ato / Singh, Simran B / Alian, Osama M / Broeker, Carson D / Zaluzec, Erin K / ONeill, Morgan / Puschner, Birgit / Sousa, Aron / Bix, Laura / Jespersen, Brian / Holzman, Claudia / Mitchell, Jade / Julien, Ryan / Askin, Yesim / Barnes, Danielle / Durshanpalli, Purna / Krum, Doug / Weber, Rett / Patterson, Morgan / Anderson, Becky / Hunt, Ryan / O'Brien, Benjamin / Umstead, Andrew / Beck, John S / Vega, Irving E / Sortwell, Caryl E / Lipton, Jack W

Journal of visualized experiments : JoVE

2022 , Issue 184

Abstract: Identification and isolation of contagious individuals along with quarantine of close contacts, is critical for slowing the spread of COVID-19. Large-scale testing in a surveillance or screening capacity for asymptomatic carriers of COVID-19 provides ... ...

Abstract	Identification and isolation of contagious individuals along with quarantine of close contacts, is critical for slowing the spread of COVID-19. Large-scale testing in a surveillance or screening capacity for asymptomatic carriers of COVID-19 provides both data on viral spread and the follow-up ability to rapidly test individuals during suspected outbreaks. The COVID-19 early detection program at Michigan State University has been utilizing large-scale testing in a surveillance or screening capacity since fall of 2020. The methods adapted here take advantage of the reliability, large sample volume, and self-collection benefits of saliva, paired with a cost-effective, reagent conserving two-dimensional pooling scheme. The process was designed to be adaptable to supply shortages, with many components of the kits and the assay easily substituted. The processes outlined for collecting and processing SARS-CoV-2 samples can be adapted to test for future viral pathogens reliably expressed in saliva. By providing this blueprint for universities or other organizations, preparedness plans for future viral outbreaks can be developed.
MeSH term(s)	COVID-19/diagnosis ; COVID-19 Testing ; Humans ; Reproducibility of Results ; SARS-CoV-2 ; Saliva ; Specimen Handling
Language	English
Publishing date	2022-06-23
Publishing country	United States
Document type	Journal Article ; Video-Audio Media ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/64008
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.

Lucas, Michaela / Ulsenheimer, Axel / Pfafferot, Katja / Heeg, Malte H J / Gaudieri, Silvana / Grüner, Norbert / Rauch, Andri / Gerlach, J Tilman / Jung, Maria-Christina / Zachoval, Reinhart / Pape, Gerd R / Schraut, Winfried / Santantonio, Teresa / Nitschko, Hans / Obermeier, Martin / Phillips, Rodney / Scriba, Thomas J / Semmo, Nasser / Day, Cheryl /

Weber, Jonathan N / Fidler, Sarah / Thimme, Robert / Haberstroh, Anita / Baumert, Thomas F / Klenerman, Paul / Diepolder, Helmut M

PloS one

2007 Volume 2, Issue 7, Page(s) e649

Abstract: Background: CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent ...

Abstract	Background: CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Methodology/principal findings: Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. Conclusions/significance: During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.
MeSH term(s)	Acute Disease ; Amino Acid Sequence ; Base Sequence ; CD4-Positive T-Lymphocytes/virology ; DNA Primers ; Epitopes, T-Lymphocyte/immunology ; Female ; Genotype ; HLA-DR1 Antigen/chemistry ; HLA-DR1 Antigen/immunology ; Hepacivirus/genetics ; Hepacivirus/isolation & purification ; Hepatitis C/immunology ; Humans ; Immunity, Cellular ; Liver/immunology ; Liver/virology ; Male ; Peptide Fragments/chemistry ; Peptide Fragments/immunology ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes, Helper-Inducer/virology ; Viral Proteins/analysis ; Viral Proteins/chemistry ; Viral Proteins/immunology
Chemical Substances	DNA Primers ; Epitopes, T-Lymphocyte ; HLA-DR1 Antigen ; Peptide Fragments ; Viral Proteins
Language	English
Publishing date	2007-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0000649
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.

Michaela Lucas / Axel Ulsenheimer / Katja Pfafferot / Malte H J Heeg / Silvana Gaudieri / Norbert Grüner / Andri Rauch / J Tilman Gerlach / Maria-Christina Jung / Reinhart Zachoval / Gerd R Pape / Winfried Schraut / Teresa Santantonio / Hans Nitschko / Martin Obermeier / Rodney Phillips / Thomas J Scriba / Nasser Semmo / Cheryl Day /

Jonathan N Weber / Sarah Fidler / Robert Thimme / Anita Haberstroh / Thomas F Baumert / Paul Klenerman / Helmut M Diepolder

PLoS ONE, Vol 2, Iss 7, p e

2007 Volume 649

Abstract: CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short- ... ...

Abstract	CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays.Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C.During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2007-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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