دورية أكاديمية
أعرض في EDS

Exploiting bacterial effector proteins to uncover evolutionarily conserved antiviral host machinery.

التفاصيل البيبلوغرافية
العنوان: Exploiting bacterial effector proteins to uncover evolutionarily conserved antiviral host machinery.
المؤلفون: Embry A; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United State of America., Baggett NS; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United State of America., Heisler DB; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United State of America., White A; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United State of America., de Jong MF; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United State of America., Kocsis BL; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United State of America., Tomchick DR; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, United State of America., Alto NM; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United State of America., Gammon DB; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, United State of America.
المصدر: PLoS pathogens [PLoS Pathog] 2024 May 16; Vol. 20 (5), pp. e1012010. Date of Electronic Publication: 2024 May 16 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Virus Replication*/physiology , Bacterial Proteins*/metabolism , Bacterial Proteins*/genetics , Host-Pathogen Interactions*, Animals ; Humans ; Arboviruses ; Shigella flexneri/pathogenicity ; Arbovirus Infections/virology ; Cell Line
مستخلص: Arboviruses are a diverse group of insect-transmitted pathogens that pose global public health challenges. Identifying evolutionarily conserved host factors that combat arbovirus replication in disparate eukaryotic hosts is important as they may tip the balance between productive and abortive viral replication, and thus determine virus host range. Here, we exploit naturally abortive arbovirus infections that we identified in lepidopteran cells and use bacterial effector proteins to uncover host factors restricting arbovirus replication. Bacterial effectors are proteins secreted by pathogenic bacteria into eukaryotic hosts cells that can inhibit antimicrobial defenses. Since bacteria and viruses can encounter common host defenses, we hypothesized that some bacterial effectors may inhibit host factors that restrict arbovirus replication in lepidopteran cells. Thus, we used bacterial effectors as molecular tools to identify host factors that restrict four distinct arboviruses in lepidopteran cells. By screening 210 effectors encoded by seven different bacterial pathogens, we identify several effectors that individually rescue the replication of all four arboviruses. We show that these effectors encode diverse enzymatic activities that are required to break arbovirus restriction. We further characterize Shigella flexneri-encoded IpaH4 as an E3 ubiquitin ligase that directly ubiquitinates two evolutionarily conserved proteins, SHOC2 and PSMC1, promoting their degradation in insect and human cells. We show that depletion of either SHOC2 or PSMC1 in insect or human cells promotes arbovirus replication, indicating that these are ancient virus restriction factors conserved across invertebrate and vertebrate hosts. Collectively, our study reveals a novel pathogen-guided approach to identify conserved antimicrobial machinery, new effector functions, and conserved roles for SHOC2 and PSMC1 in virus restriction.
Competing Interests: The authors declare that there are no competing interests.
(Copyright: © 2024 Embry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
التعليقات: Update of: bioRxiv. 2024 Jan 30;:. (PMID: 38352400)
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معلومات مُعتمدة: R01 AI083359 United States AI NIAID NIH HHS; R21 AI169558 United States AI NIAID NIH HHS; R35 GM137978 United States GM NIGMS NIH HHS; T32 AI007520 United States AI NIAID NIH HHS
تواريخ الأحداث: Date Created: 20240516 Date Completed: 20240516 Latest Revision: 20240527
رمز التحديث: 20240527
مُعرف محوري في PubMed: PMC11098378
DOI: 10.1371/journal.ppat.1012010
PMID: 38753575
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1012010