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  1. Article ; Online: Defective viral RNA sensing linked to severe COVID-19.

    Schoggins, John

    Science (New York, N.Y.)

    2021  Volume 374, Issue 6567, Page(s) 535–536

    Abstract: Genetic variation in a sensor of double-stranded RNA can exacerbate COVID-19. ...

    Abstract Genetic variation in a sensor of double-stranded RNA can exacerbate COVID-19.
    MeSH term(s) COVID-19 ; Humans ; RNA, Viral/genetics ; SARS-CoV-2
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2021-10-28
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abm3921
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  2. Article ; Online: Interferon-Stimulated Genes: What Do They All Do?

    Schoggins, John W

    Annual review of virology

    2019  Volume 6, Issue 1, Page(s) 567–584

    Abstract: In the absence of an intact interferon (IFN) response, mammals may be susceptible to lethal viral infection. IFNs are secreted cytokines that activate a signal transduction cascade leading to the induction of hundreds of interferon-stimulated genes (ISGs) ...

    Abstract In the absence of an intact interferon (IFN) response, mammals may be susceptible to lethal viral infection. IFNs are secreted cytokines that activate a signal transduction cascade leading to the induction of hundreds of interferon-stimulated genes (ISGs). Remarkably, approximately 10% of the genes in the human genome have the potential to be regulated by IFNs. What do all of these genes do? It is a complex question without a simple answer. From decades of research, we know that many of the protein products encoded by these ISGs work alone or in concert to achieve one or more cellular outcomes, including antiviral defense, antiproliferative activities, and stimulation of adaptive immunity. The focus of this review is the antiviral activities of the IFN/ISG system. This includes general paradigms of ISG function, supported by specific examples in the literature, as well as methodologies to identify and characterize ISG function.
    MeSH term(s) Animals ; Humans ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/immunology ; Interferons/genetics ; Interferons/immunology ; Virus Diseases/genetics ; Virus Diseases/immunology ; Virus Diseases/virology ; Virus Physiological Phenomena ; Viruses/genetics
    Chemical Substances Interferon Regulatory Factors ; Interferons (9008-11-1)
    Language English
    Publishing date 2019-07-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2764224-0
    ISSN 2327-0578 ; 2327-056X
    ISSN (online) 2327-0578
    ISSN 2327-056X
    DOI 10.1146/annurev-virology-092818-015756
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  3. Article: IRF7 from the black flying fox induces a STAT1-independent ISG response in unstimulated cell lines that protects against diverse RNA viruses.

    Cruz-Rivera, Pamela C De La / Eitson, Jennifer L / Schoggins, John W

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Bats are considered unique in their ability to harbor large numbers of viruses and serve as reservoirs for zoonotic viruses that have the potential to spill over into humans. However, these animals appear relatively resistant to the pathogenic effects of ...

    Abstract Bats are considered unique in their ability to harbor large numbers of viruses and serve as reservoirs for zoonotic viruses that have the potential to spill over into humans. However, these animals appear relatively resistant to the pathogenic effects of many viruses. Mounting evidence suggests that bats may tolerate viral infections due to unique immune features. These include evolutionary innovations in inflammatory pathways and in the molecules involved in viral sensing, interferon induction, and downstream interferon-induced antiviral effectors. We sought to determine whether interferon-stimulated genes (ISGs) from the black flying fox (
    Language English
    Publishing date 2024-05-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.05.02.592239
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  4. Article: Recent advances in antiviral interferon-stimulated gene biology.

    Schoggins, John W

    F1000Research

    2018  Volume 7, Page(s) 309

    Abstract: The interferon response protects cells from invading viral pathogens by transcriptionally inducing the expression of interferon-stimulated genes (ISGs), some of which encode effectors with varied antiviral functions. As screening technologies improve and ...

    Abstract The interferon response protects cells from invading viral pathogens by transcriptionally inducing the expression of interferon-stimulated genes (ISGs), some of which encode effectors with varied antiviral functions. As screening technologies improve and mouse model development quickens, more ISGs are continually being identified, characterized mechanistically, and evaluated for protective roles
    Language English
    Publishing date 2018-03-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2699932-8
    ISSN 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.12450.1
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  5. Article ; Online: Enterovirus 3C Protease Cleaves TRIM7 To Dampen Its Antiviral Activity.

    Fan, Wenchun / McDougal, Matthew B / Schoggins, John W

    Journal of virology

    2022  Volume 96, Issue 19, Page(s) e0133222

    Abstract: Mammalian TRIM7 is an antiviral protein that inhibits multiple human enteroviruses by degrading the viral 2BC protein. Whether TRIM7 is reciprocally targeted by enteroviruses is not known. Here, we report that the 3C protease (3Cpro) from two ... ...

    Abstract Mammalian TRIM7 is an antiviral protein that inhibits multiple human enteroviruses by degrading the viral 2BC protein. Whether TRIM7 is reciprocally targeted by enteroviruses is not known. Here, we report that the 3C protease (3Cpro) from two enteroviruses, coxsackievirus B3 (CVB3) and poliovirus, targets TRIM7 for cleavage. CVB3 3Cpro cleaves TRIM7 at glutamine 24 (Q24), resulting in a truncated TRIM7 that fails to inhibit CVB3 due to dampened E3 ubiquitin ligase activity. TRIM7 Q24 is highly conserved across mammals, except in marsupials, which instead have a naturally occurring histidine (H24) that is not subject to 3Cpro cleavage. Marsupials also express two isoforms of TRIM7, and the two proteins from koalas have distinct antiviral activities. The longer isoform contains an additional exon due to alternate splice site usage. This additional exon contains a unique 3Cpro cleavage site, suggesting that certain enteroviruses may have evolved to target marsupial TRIM7 even if the canonical Q24 is missing. Combined with computational analyses indicating that TRIM7 is rapidly evolving, our data raise the possibility that TRIM7 may be targeted by enterovirus evasion strategies and that evolution of TRIM7 across mammals may have conferred unique antiviral properties.
    MeSH term(s) 3C Viral Proteases/metabolism ; Animals ; Enterovirus/enzymology ; Enterovirus Infections ; Glutamine ; Histidine ; Host-Pathogen Interactions ; Phascolarctidae/virology ; Tripartite Motif Proteins/metabolism ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances Tripartite Motif Proteins ; Glutamine (0RH81L854J) ; Histidine (4QD397987E) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; 3C Viral Proteases (EC 3.4.22.28)
    Language English
    Publishing date 2022-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.01332-22
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  6. Article ; Online: IMMUNOLOGY. Viruses carry antiviral cargo.

    Schoggins, John W

    Science (New York, N.Y.)

    2015  Volume 349, Issue 6253, Page(s) 1166–1167

    MeSH term(s) Animals ; Dendritic Cells/immunology ; HIV Infections/immunology ; HIV-1/metabolism ; Herpes Simplex/immunology ; Herpesviridae Infections/immunology ; Herpesvirus 1, Human/metabolism ; Humans ; Immunity, Innate/immunology ; Interferon-beta/immunology ; Muromegalovirus/metabolism ; Nucleotides, Cyclic/metabolism ; Second Messenger Systems ; Vaccinia/immunology ; Vaccinia virus/metabolism ; Virion/metabolism
    Chemical Substances Nucleotides, Cyclic ; Interferon-beta (77238-31-4)
    Language English
    Publishing date 2015-09-11
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aad0942
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  7. Article ; Online: A phospholipase linkAGE to SARS susceptibility.

    Schoggins, John W

    The Journal of experimental medicine

    2015  Volume 212, Issue 11, Page(s) 1755

    MeSH term(s) Animals ; Disease Susceptibility ; Group II Phospholipases A2/physiology ; Humans ; Severe Acute Respiratory Syndrome/etiology
    Chemical Substances Group II Phospholipases A2 (EC 3.1.1.4)
    Keywords covid19
    Language English
    Publishing date 2015-10-19
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.21211insight2
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  8. Article ; Online: A Sense of Self: RIG-I's Tolerance to Host RNA.

    Schoggins, John W

    Immunity

    2015  Volume 43, Issue 1, Page(s) 1–2

    Abstract: The innate immune sensor RIG-I recognizes viral RNA while avoiding unwanted activation by self RNA. In this issue of Immunity, Schuberth-Wagner et al. (2015) show that a histidine residue in the RNA binding pocket of RIG-I sterically excludes the cap1 ... ...

    Abstract The innate immune sensor RIG-I recognizes viral RNA while avoiding unwanted activation by self RNA. In this issue of Immunity, Schuberth-Wagner et al. (2015) show that a histidine residue in the RNA binding pocket of RIG-I sterically excludes the cap1 structure of self RNA, thereby preventing downstream activation.
    MeSH term(s) Animals ; DEAD-box RNA Helicases/genetics ; Humans ; Immune Tolerance/genetics ; RNA/genetics ; RNA Processing, Post-Transcriptional/genetics ; Yellow fever virus/enzymology
    Chemical Substances RNA (63231-63-0) ; DEAD-box RNA Helicases (EC 3.6.4.13)
    Language English
    Publishing date 2015-07-21
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2015.06.022
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  9. Article ; Online: Functional-genomic analysis reveals intraspecies diversification of antiviral receptor transporter proteins in Xenopus laevis.

    Boys, Ian N / Mar, Katrina B / Schoggins, John W

    PLoS genetics

    2021  Volume 17, Issue 5, Page(s) e1009578

    Abstract: The Receptor Transporter Protein (RTP) family is present in most, if not all jawed vertebrates. Most of our knowledge of this protein family comes from studies on mammalian RTPs, which are multi-function proteins that regulate cell-surface G-protein ... ...

    Abstract The Receptor Transporter Protein (RTP) family is present in most, if not all jawed vertebrates. Most of our knowledge of this protein family comes from studies on mammalian RTPs, which are multi-function proteins that regulate cell-surface G-protein coupled receptor levels, influence olfactory system development, regulate immune signaling, and directly inhibit viral infection. However, mammals comprise less than one-tenth of extant vertebrate species, and our knowledge about the expression, function, and evolution of non-mammalian RTPs is limited. Here, we explore the evolutionary history of RTPs in vertebrates. We identify signatures of positive selection in many vertebrate RTP clades and characterize multiple, independent expansions of the RTP family outside of what has been described in mammals. We find a striking expansion of RTPs in the African clawed frog, Xenopus laevis, with 11 RTPs in this species as opposed to 1 to 4 in most other species. RNA sequencing revealed that most X. laevis RTPs are upregulated following immune stimulation. In functional assays, we demonstrate that at least three of these X. laevis RTPs inhibit infection by RNA viruses, suggesting that RTP homologs may serve as antiviral effectors outside of Mammalia.
    MeSH term(s) Animals ; Antiviral Agents/immunology ; Evolution, Molecular ; Genomics ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/immunology ; Poly I-C/immunology ; Synteny ; Xenopus Proteins/genetics ; Xenopus Proteins/immunology ; Xenopus laevis/genetics ; Xenopus laevis/immunology ; Xenopus laevis/metabolism
    Chemical Substances Antiviral Agents ; Membrane Transport Proteins ; Xenopus Proteins ; Poly I-C (O84C90HH2L)
    Language English
    Publishing date 2021-05-20
    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.
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009578
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  10. Article ; Online: Comparative analysis of viral entry for Asian and African lineages of Zika virus.

    Rinkenberger, Nicholas / Schoggins, John W

    Virology

    2019  Volume 533, Page(s) 59–67

    Abstract: Zika virus (ZIKV) is an emerging pathogen with global health and economic impacts. ZIKV circulates as two major lineages, Asian or African. The Asian lineage has recently been associated with significant disease in humans. Numerous studies have revealed ... ...

    Abstract Zika virus (ZIKV) is an emerging pathogen with global health and economic impacts. ZIKV circulates as two major lineages, Asian or African. The Asian lineage has recently been associated with significant disease in humans. Numerous studies have revealed differences between African and Asian ZIKV strains with respect to cellular infectivity, pathogenesis, and immune activation. Less is known about the mechanism of ZIKV entry and whether viral entry differs between strains. Here, we characterized ZIKV entry with two Asian and two African strains. All viruses exhibited a requirement for clathrin-mediated endocytosis and Rab5a function. Additionally, all ZIKV strains tested were sensitive to pH in the range of 6.5-6.1 and were reliant on endosomal acidification for infection. Finally, we provide direct evidence that ZIKV primarily fuses with late endosomes. These findings contribute new insight into the ZIKV entry process and suggest that divergent ZIKV strains enter cells in a highly conserved manner.
    MeSH term(s) Africa ; Asia ; Endocytosis ; Endosomes/virology ; Humans ; Virus Internalization ; Zika Virus/classification ; Zika Virus/genetics ; Zika Virus/physiology ; Zika Virus Infection/physiopathology ; Zika Virus Infection/virology
    Language English
    Publishing date 2019-04-25
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2019.04.008
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