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  1. Article ; Online: Game over for RSV?

    Strine, Madison S / Wilen, Craig B

    Science immunology

    2023  Volume 8, Issue 84, Page(s) eadi8764

    Abstract: Passive immunization with nirsevimab protects infants from severe RSV disease without impairing the immune response to natural infection. ...

    Abstract Passive immunization with nirsevimab protects infants from severe RSV disease without impairing the immune response to natural infection.
    MeSH term(s) Infant ; Humans ; Respiratory Syncytial Virus Infections/prevention & control ; Immunization, Passive
    Language English
    Publishing date 2023-06-02
    Publishing country United States
    Document type Journal Article ; Comment
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.adi8764
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Tuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces.

    Strine, Madison S / Wilen, Craig B

    PLoS pathogens

    2022  Volume 18, Issue 3, Page(s) e1010318

    Abstract: Although tuft cells were discovered over 60 years ago, their functions have long been enigmatic, especially in human health. Nonetheless, tuft cells have recently emerged as key orchestrators of the host response to diverse microbial infections in the ... ...

    Abstract Although tuft cells were discovered over 60 years ago, their functions have long been enigmatic, especially in human health. Nonetheless, tuft cells have recently emerged as key orchestrators of the host response to diverse microbial infections in the gut and airway. While tuft cells are epithelial in origin, they exhibit functions akin to immune cells and mediate important interkingdom interactions between the host and helminths, protists, viruses, and bacteria. With broad intra- and intertissue heterogeneity, tuft cells sense and respond to microbes with exquisite specificity. Tuft cells can recognize helminth and protist infection, driving a type 2 immune response to promote parasite expulsion. Tuft cells also serve as the primary physiologic target of persistent murine norovirus (MNV) and promote immune evasion. Recently, tuft cells were also shown to be infected by rotavirus. Other viral infections, such as influenza A virus, can induce tuft cell-dependent tissue repair. In the context of coinfection, tuft cells promote neurotropic flavivirus replication by dampening antiviral adaptive immune responses. Commensal and pathogenic bacteria can regulate tuft cell abundance and function and, in turn, tuft cells are implicated in modulating bacterial infiltration and mucosal barrier integrity. However, the contribution of tuft cells to microbial sensing in humans and their resulting effector responses are poorly characterized. Herein, we aim to provide a comprehensive overview of microbial activation of tuft cells with an emphasis on tuft cell heterogeneity and differences between mouse and human tuft cell biology as it pertains to human health and disease.
    MeSH term(s) Animals ; Intestinal Mucosa ; Mice ; Norovirus ; Parasites
    Language English
    Publishing date 2022-03-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010318
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB-dependent IFITM3 expression.

    Munir, Moiz / Embry, Aaron / Doench, John G / Heaton, Nicholas S / Wilen, Craig B / Orchard, Robert C

    The Journal of biological chemistry

    2024  Volume 300, Issue 4, Page(s) 107153

    Abstract: The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape, we conducted a gain-of-function, genome-wide CRISPR activation screen with influenza A virus. We ... ...

    Abstract The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape, we conducted a gain-of-function, genome-wide CRISPR activation screen with influenza A virus. We identified both appreciated and novel antiviral genes, including Jade family PHD zinc finger 3 (JADE3) a protein involved in directing the histone acetyltransferase histone acetyltransferase binding to ORC1 complex to modify chromatin and regulate transcription. JADE3 is both necessary and sufficient to restrict influenza A virus infection. Our results suggest a distinct function for JADE3 as expression of the closely related paralogs JADE1 and JADE2 does not confer resistance to influenza A virus infection. JADE3 is required for both constitutive and inducible expression of the well-characterized antiviral gene interferon-induced transmembrane protein 3 (IFITM3). Furthermore, we find JADE3 activates the NF-kB signaling pathway, which is required for the promotion of IFITM3 expression by JADE3. Therefore, we propose JADE3 activates an antiviral genetic program involving NF-kB-dependent IFITM3 expression to restrict influenza A virus infection.
    MeSH term(s) Animals ; Humans ; CRISPR-Cas Systems ; Gene Expression Regulation/genetics ; Gene Expression Regulation/immunology ; HEK293 Cells ; Immunity, Innate/genetics ; Influenza A virus/immunology ; Influenza, Human/immunology ; Membrane Proteins/genetics ; Membrane Proteins/immunology ; NF-kappa B/genetics ; NF-kappa B/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/immunology ; Signal Transduction ; Oncogene Proteins/genetics ; Oncogene Proteins/immunology
    Chemical Substances IFITM3 protein, human ; Membrane Proteins ; NF-kappa B ; RNA-Binding Proteins ; JADE3 protein, human ; Oncogene Proteins
    Language English
    Publishing date 2024-03-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2024.107153
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Interpretation of SARS-CoV-2 Diagnostic Tests.

    Stites, Edward C / Wilen, Craig B

    Med (New York, N.Y.)

    2020  Volume 1, Issue 1, Page(s) 78–89

    Abstract: Testing for SARS-CoV-2 has attracted a tremendous amount of attention as a tool to manage the ongoing COVID-19 pandemic. Although diagnostic laboratory testing is used ubiquitously by physicians and encountered regularly by individuals receiving medical ... ...

    Abstract Testing for SARS-CoV-2 has attracted a tremendous amount of attention as a tool to manage the ongoing COVID-19 pandemic. Although diagnostic laboratory testing is used ubiquitously by physicians and encountered regularly by individuals receiving medical care, several aspects of test interpretation are incompletely understood by medical communities and the general population, creating a significant challenge in minimizing the damage caused by disease spread through informed decision making and proper testing utilization. Here, general principles of test interpretation are reviewed and applied to specific examples, such as whether asymptomatic individuals should be tested, what it means to test positive (or negative), and how to interpret tests for "immunity passports." Unexpectedly, the answers seem to run contrary to many of the popular narratives about testing as a tool for managing COVID-19. Although testing is an important and essential part of managing diseases such as COVID-19, improper utilization can have unintended negative consequences.
    MeSH term(s) COVID-19/diagnosis ; COVID-19 Testing ; Clinical Laboratory Techniques ; Diagnostic Tests, Routine ; Humans ; Pandemics ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-08-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ISSN 2666-6340
    ISSN (online) 2666-6340
    DOI 10.1016/j.medj.2020.08.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB.

    Munir, Moiz / Embry, Aaron / Doench, John G / Heaton, Nicholas S / Wilen, Craig B / Orchard, Robert C

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape we conducted a gain of function, genome-wide CRISPR activation screen with influenza A virus. We ... ...

    Abstract The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape we conducted a gain of function, genome-wide CRISPR activation screen with influenza A virus. We identified both appreciated and novel antiviral genes, including JADE3 a protein involved in directing the histone acetyltransferase HBO1 complex to modify chromatin and regulate transcription. JADE3 is both necessary and sufficient to restrict influenza A virus infection. Interestingly, expression of the closely related paralogues JADE1 and JADE2 are unable to restrict influenza A virus infection, suggesting a distinct function of JADE3. We identify both shared and unique transcriptional signatures between uninfected cells expressing JADE3 and JADE2. These data provide a framework for understanding the overlapping and distinct functions of the JADE family of paralogues. Specifically, we find that JADE3 expression activates the NF-kB signaling pathway, consistent with an antiviral function. Therefore, we propose JADE3, but not JADE1 or JADE2, activates an antiviral genetic program involving the NF-kB pathway to restrict influenza A virus infection.
    Language English
    Publishing date 2023-09-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.29.560128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Age-associated features of norovirus infection analysed in mice.

    Kennedy, Elizabeth A / Aggarwal, Somya / Dhar, Arko / Karst, Stephanie M / Wilen, Craig B / Baldridge, Megan T

    Nature microbiology

    2023  Volume 8, Issue 6, Page(s) 1095–1107

    Abstract: Norovirus (NoV) is the leading global cause of viral gastroenteritis. Young children bear the highest burden of disease and play a key role in viral transmission throughout the population. However, which host factors contribute to age-associated ... ...

    Abstract Norovirus (NoV) is the leading global cause of viral gastroenteritis. Young children bear the highest burden of disease and play a key role in viral transmission throughout the population. However, which host factors contribute to age-associated variability in NoV severity and shedding are not well-defined. The murine NoV (MNoV) strain CR6 causes persistent infection in adult mice and targets intestinal tuft cells. Here we find that natural transmission of CR6 from infected dams occurred only in juvenile mice. Direct oral CR6 inoculation of wild-type neonatal mice led to accumulation of viral RNA in the ileum and prolonged shedding in the stool that was replication-independent. This viral exposure induced both innate and adaptive immune responses including interferon-stimulated gene expression and MNoV-specific antibody responses. Interestingly, viral uptake depended on passive ileal absorption of luminal virus, a process blocked by cortisone acetate administration, which prevented ileal viral RNA accumulation. Neonates lacking interferon signalling in haematopoietic cells were susceptible to productive infection, viral dissemination and lethality, which depended on the canonical MNoV receptor CD300LF. Together, our findings reveal developmentally associated aspects of persistent MNoV infection, including distinct tissue and cellular tropism, mechanisms of interferon regulation and severity of infection in the absence of interferon signalling. These emphasize the importance of defining viral pathogenesis phenotypes across the developmental spectrum and highlight passive viral uptake as an important contributor to enteric infections in early life.
    MeSH term(s) Mice ; Animals ; Interferons ; Intestines ; Intestine, Small/metabolism ; Norovirus ; Caliciviridae Infections
    Chemical Substances Interferons (9008-11-1)
    Language English
    Publishing date 2023-05-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-023-01383-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: The Interpretation of SARS-CoV-2 Diagnostic Tests

    Stites, Edward C / Wilen, Craig B

    Abstract: Testing for SARS-CoV-2 has attracted a tremendous amount of attention as a tool to manage the ongoing COVID-19 pandemic. Although diagnostic laboratory testing is utilized ubiquitously by physicians and encountered regularly by individuals receiving ... ...

    Abstract Testing for SARS-CoV-2 has attracted a tremendous amount of attention as a tool to manage the ongoing COVID-19 pandemic. Although diagnostic laboratory testing is utilized ubiquitously by physicians and encountered regularly by individuals receiving medical care, several aspects of test interpretation are incompletely understood by medical communities and the general population, creating a significant challenge in minimizing the damage caused by disease spread through informed decision making and proper testing utilization. Here, general principles of test interpretation are reviewed and applied to specific examples, such as whether asymptomatic individuals should be tested, what it means to test positive (or negative), and how to interpret tests for "immunity passports". Unexpectedly, the answers seem to run contrary to many of the popular narratives about testing as a tool for managing COVID-19. Although testing is an important and essential part of managing diseases like COVID-19, improper utilization can potentially have unintended negative consequences.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #726690
    Database COVID19

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  8. Article ; Online: The Interpretation of SARS-CoV-2 Diagnostic Tests

    Stites, Edward C. / Wilen, Craig B.

    Med ; ISSN 2666-6340

    2020  

    Keywords covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    DOI 10.1016/j.medj.2020.08.001
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  9. Article ; Online: Systematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq.

    Patel, Shivali / Sexton, Alec N / Strine, Madison S / Wilen, Craig B / Simon, Matthew D / Pyle, Anna Marie

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 3426

    Abstract: Compact RNA structural motifs control many aspects of gene expression, but we lack methods for finding these structures in the vast expanse of multi-kilobase RNAs. To adopt specific 3-D shapes, many RNA modules must compress their RNA backbones together, ...

    Abstract Compact RNA structural motifs control many aspects of gene expression, but we lack methods for finding these structures in the vast expanse of multi-kilobase RNAs. To adopt specific 3-D shapes, many RNA modules must compress their RNA backbones together, bringing negatively charged phosphates into close proximity. This is often accomplished by recruiting multivalent cations (usually Mg
    MeSH term(s) Nucleic Acid Conformation ; RNA/metabolism ; Terbium/metabolism ; Terbium/pharmacology ; Nucleotide Motifs ; Cations
    Chemical Substances RNA (63231-63-0) ; Terbium (06SSF7P179) ; Cations
    Language English
    Publishing date 2023-06-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; 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/s41467-023-38623-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Norovirus Attachment and Entry

    Graziano, Vincent R / Wei, Jin / Wilen, Craig B

    Viruses. 2019 May 30, v. 11, no. 6

    2019  

    Abstract: Human norovirus is a major human pathogen causing the majority of cases of viral gastroenteritis globally. Viral entry is the first step of the viral life cycle and is a significant determinant of cell tropism, host range, immune interactions, and ... ...

    Abstract Human norovirus is a major human pathogen causing the majority of cases of viral gastroenteritis globally. Viral entry is the first step of the viral life cycle and is a significant determinant of cell tropism, host range, immune interactions, and pathogenesis. Bile salts and histo-blood group antigens are key mediators of norovirus entry; however, the molecular mechanisms by which these molecules promote infection and the identity of a potential human norovirus receptor remain unknown. Recently, there have been several important advances in norovirus entry biology including the identification of CD300lf as the receptor for murine norovirus and of the role of the minor capsid protein VP2 in viral genome release. Here, we will review the current understanding about norovirus attachment and entry and highlight important future directions.
    Keywords Norovirus ; animal viruses ; antigens ; bile salts ; coat proteins ; genome ; host range ; pathogenesis ; viral gastroenteritis
    Language English
    Dates of publication 2019-0530
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v11060495
    Database NAL-Catalogue (AGRICOLA)

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