DOCSLIB.ORG

Computational and Experimental Analysis of TAL Effector-DNA Binding Erin Lynn Doyle Iowa State University

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Computational and Experimental Analysis of TAL Effector-DNA Binding Erin Lynn Doyle Iowa State University Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2013 Computational and experimental analysis of TAL effector-DNA binding Erin Lynn Doyle Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Agricultural Science Commons, Agriculture Commons, Bioinformatics Commons, Biology Commons, and the Plant Pathology Commons Recommended Citation Doyle, Erin Lynn, "Computational and experimental analysis of TAL effector-DNA binding" (2013). Graduate Theses and Dissertations. 13132. https://lib.dr.iastate.edu/etd/13132 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Computational and experimental analysis of TAL effector-DNA binding by Erin Lynn Doyle A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Bioinformatics and Computational Biology Program of Study Committee: Adam J. Bogdanove, Co-Major Professor Daniel Nettleton, Co-Major Professor Susan Lamont Leonor Leandro Steve Whitham Iowa State University Ames, Iowa 2013 Copyright © Erin Lynn Doyle, 2013. All rights reserved. ii TABLE OF CONTENTS LIST OF FIGURES ................................................................................................................... vii LIST OF TABLES ....................................................................................................................... ix ABSTRACT ................................................................................................................................. x CHAPTER 1. GENERAL INTRODUCTION ................................................................................ 1 Abbreviations .......................................................................................................................... 1 Introduction ............................................................................................................................ 1 Rationale ................................................................................................................................ 2 Dissertation Organization ....................................................................................................... 3 References ............................................................................................................................. 5 CHAPTER 2. THE EFFECTS OF TAL EFFECTORS ON CELL BIOLOGY .............................. 7 Abstract .................................................................................................................................. 7 Introduction ............................................................................................................................ 7 TAL effector structure and function ......................................................................................... 8 The natural role of TAL effectors ...........................................................................................11 TAL effectors and improving plant disease resistance ...........................................................13 TAL effectors as customizable DNA targeting proteins ..........................................................14 Fusions for targeted gene activation and repression ..........................................................14 TAL effector fusions for genome editing .............................................................................15 Design and construction .....................................................................................................17 Future challenges ..................................................................................................................17 References ............................................................................................................................19 CHAPTER 3. EFFICIENT DESIGN AND ASSEMBLY OF CUSTOM TALEN AND OTHER TAL EFFECTOR-BASED CONSTRUCTS FOR DNA TARGETING ..........................................25 Abstract .................................................................................................................................25 Introduction ...........................................................................................................................26 Materials and Methods ..........................................................................................................29 Protocol for assembly of custom TALEN, TAL effector or TAL effector fusion-ready constructs ..........................................................................................................................29 Construction of module, last repeat, array, and backbone plasmids ...................................31 iii Software to identify candidate TALEN target sites ..............................................................33 Testing TALEN function in yeast ........................................................................................34 Expression of custom TALENs in human cells and Arabidopsis protoplasts and detection of site-specific mutations.....................................................................................35 Expression of a custom TAL effector in Xanthomonas and in planta activity assay ............36 Results ..................................................................................................................................36 Efficient assembly of custom repeat arrays into TALEN and other TAL effector-based constructs ..........................................................................................................................36 Guidelines and software for TALEN site selection and repeat array design. .......................37 Activity of custom TALENs in a yeast-based DNA cleavage assay ....................................39 Targeted mutagenesis in human cells and Arabidopsis protoplasts using custom TALENs .............................................................................................................................39 Replication of AvrHah1 TAL effector activity with a Golden Gate assembled clone ............40 Discussion .............................................................................................................................41 Acknowledgements ...............................................................................................................44 Funding .................................................................................................................................44 References ............................................................................................................................45 Supplementary Material .........................................................................................................47 CHAPTER 4. TAL EFFECTOR-NUCLEOTIDE TARGETER (TALE-NT) 2.0: TOOLS FOR TAL EFFECTOR DESIGN AND TARGET PREDICTION ..........................................................53 Abstract .................................................................................................................................53 Introduction ...........................................................................................................................53 Software and Algorithms .......................................................................................................56 Programming .....................................................................................................................56 Tools for designing custom TALENs and TAL effectors .....................................................56 A tool for identifying candidate TAL effector targets ...........................................................56 Web Interface ........................................................................................................................57 Design and general features ..............................................................................................57 TALEN Targeter .................................................................................................................58 TAL Effector Targeter.........................................................................................................59 Target Finder .....................................................................................................................59 Conclusion ............................................................................................................................61 Acknowledgements ...............................................................................................................62 iv Funding .................................................................................................................................62 References ............................................................................................................................62 Supplementary Material .........................................................................................................64 The Target Finder scoring function ....................................................................................64 References
Load more

Recommended publications
  • Allosteric Regulation in Drug Design
    Mini Review Curr Trends Biomedical Eng & Biosci Volume 4 Issue 1 - May 2017 Copyright © All rights are reserved by Ashfaq Ur Rehman DOI: 10.19080/CTBEB.2017.04.5555630 Allosteric regulation in drug design Ashfaq Ur Rehman1,2*, Shah Saud3, Nasir Ahmad4, Abdul Wadood2 and R Hamid5 1State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, China 2Department of Biochemistry, Abdul Wali Khan University Mardan, Pakistan 3Laboratory of Analytical Biochemistry and Bio separation, Shanghai Jiao Tong University, China 4Department of Chemistry, Islama College University Peshawar, Pakistan 5Department of Bioinformatics, Muhammad Ali Jinnah University Islamabad, Pakistan Submission: May 02, 2017; Published: May 23, 2017 *Corresponding author: Ashfaq Ur Rehman, State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China, Tel: ; Fax: 86-21-34204348; Email: Abstract mechanism, which are initiated through attachment of ligand or inhibitors with the protein or enzymes other than active (orthosteric) sites. ThisProtein mini review and enzymes involved play mechanism, significant types roles and in importancebiological processes of allosteric of all regulations living organisms; in drug theirdesign functions process. are regulated through allosteric Keywords: Allosteric, Activator: Drug design Introduction and ultimately cause disease. While various biological processes expressed the control at different points in life time of protein function is pivotal. As all the cell processes are under carful For the survival of all organisms the significance of protein included regulation of gene expression, translation into protein control and if not properly controls this leads to the abnormality through control of activity and at last degradation of protein [1].
    [Show full text]
  • Technical Document for Bacteriophages of Xanthomonas Campestris Pv. Vesicatoria Also Referred to As a BRAD
    US Environmental Protection Agency Office of Pesticide Programs BIOPESTICIDES REGISTRATION ACTION DOCUMENT (Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. tomato specific Bacteriophages ) (Chemical PC Codes 006449 and 006521) Xanthomonas campestris pv. vesicatoria and Pseduomonas syringae pv. tomato specific bacteriophages •••••••••••••••••••••••• BIOPESTICIDES REGISTRATION ACTION DOCUMENT (Xanthomonas campestris pv. vesicatoria and Pseudomonas syringae pv. tomato specific Bacteriophages ) (Chemical PC Codes 006449 and 006521) U.S. Environmental Protection Agency Office of Pesticide Programs Biopesticides and Pollution Prevention Division Xanthomonas campestris pv. vesicatoria and Pseduomonas syringae pv. tomato specific bacteriophages TABLE OF CONTENTS I. EXECUTIVE SUMMARY .............................................................................................Page3 II. OVERVIEW............................................................................................................................4 A. Use Profile.....................................................................................................................4 B. Regulatory History ......................................................................................................4 III. SCIENCE ASSESSMENT ....................................................................................................4 A. Physical and Chemical Properties Assessment .........................................................4 1. Product Identity and Mode
    [Show full text]
  • Design Principles for Regulator Gene Expression in a Repressible Gene
    Design of Repressible Gene Circuits: M.E. Wall et al. 1 Design Principles for Regulator Gene Expression in a Repressible Gene Circuit Michael E. Wall1,2, William S. Hlavacek3* and Michael A. Savageau4+ 1Computer and Computational Sciences Division and 2Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA 3Theoretical Biology and Biophysics Group (T-10), Theoretical Division, Mail Stop K710, Los Alamos National Laboratory, Los Alamos, NM 87545, USA 4Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA +Current address: Department of Biomedical Engineering, One Shields Avenue, University of California, Davis, CA 95616, USA. *Corresponding author Tel.: +1-505 665 1355 Fax: +1-505 665 3493 E-mail address of the corresponding author: [email protected] Design of Repressible Gene Circuits: M.E. Wall et al. 2 Summary We consider the design of a type of repressible gene circuit that is common in bacteria. In this type of circuit, a regulator protein acts to coordinately repress the expression of effector genes when a signal molecule with which it interacts is present. The regulator protein can also independently influence the expression of its own gene, such that regulator gene expression is repressible (like effector genes), constitutive, or inducible. Thus, a signal-directed change in the activity of the regulator protein can result in one of three patterns of coupled regulator and effector gene expression: direct coupling, in which regulator and effector gene expression change in the same direction; uncoupling, in which regulator gene expression remains constant while effector gene expression changes; or inverse coupling, in which regulator and effector gene expression change in opposite directions.
    [Show full text]
  • The Roles of TAL Effectors in Nature in Relation to Their Unique Properties As DNA-Targeting Tools
    The Roles of TAL Effectors in Nature in Relation to their Unique Properties as DNA-Targeting Tools Adam Bogdanove Cornell University Ithaca, New York [email protected] I will present perspectives on the unique properties of TAL effectors as DNA-targeting tools, and what we can gain from understanding how they work in nature and in plant disease. I’ll begin by comparing and contrasting the CRISPR/Cas9 and TAL-effector nuclease (TALEN) systems to highlight some of the unique features of the latter (Figure 1). TAL-effector nucleases work as dimer proteins. Each individual monomer of the TAL-ef- fector domain is about 102 kDa. Targets are encoded by repeats in each protein. In contrast with CRISPRs, typically you need one dimer per target, so it’s not readily multiplexed, certainly not as readily as the CRISPR/Cas9. The targeting specificity is typically 15 to 20 bases times 2. Therefore, on the surface, in these base configurations, TAL effectors inherently have great specificity, but, as we heard from Dan Voytas1 and Ann Ran2, a number of tricks have been applied within the CRISPR/Cas9 architecture to improve their specificity. So, they are complementary, effective systems. 1Pages 29–37. 2Pages 69–81. 3 Figure 1. Comparison of DNA-targeting systems. (Images adopted from van der Oost, 2013) TALEN Utility I was interested to see what would happen in the genome-editing field as CRISPRs gained momentum with possibly less emphasis on TAL effectors. However, a proliferation of TALEN kits have been deposited with Addgene3—which Dan Voytas4 and I are familiar with because we deposited there—and over 1,400 requests have been filled for our kit.
    [Show full text]
  • Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
    Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A.
    [Show full text]
  • Bacterial Diseases of Bananas and Enset: Current State of Knowledge and Integrated Approaches Toward Sustainable Management G
    Bacterial Diseases of Bananas and Enset: Current State of Knowledge and Integrated Approaches Toward Sustainable Management G. Blomme, M. Dita, K. S. Jacobsen, L. P. Vicente, A. Molina, W. Ocimati, Stéphane Poussier, Philippe Prior To cite this version: G. Blomme, M. Dita, K. S. Jacobsen, L. P. Vicente, A. Molina, et al.. Bacterial Diseases of Bananas and Enset: Current State of Knowledge and Integrated Approaches Toward Sustainable Management. Frontiers in Plant Science, Frontiers, 2017, 8, pp.1-25. 10.3389/fpls.2017.01290. hal-01608050 HAL Id: hal-01608050 https://hal.archives-ouvertes.fr/hal-01608050 Submitted on 28 Aug 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License fpls-08-01290 July 22, 2017 Time: 11:6 # 1 REVIEW published: 20 July 2017 doi: 10.3389/fpls.2017.01290 Bacterial Diseases of Bananas and Enset: Current State of Knowledge and Integrated Approaches Toward Sustainable Management Guy Blomme1*, Miguel Dita2, Kim Sarah Jacobsen3, Luis Pérez Vicente4, Agustin
    [Show full text]
  • Xanthomonas Leaf Spot of Roses
    EPLP-026 7/18 Xanthomonas Leaf Spot of Roses Madalyn Shires, Extension Graduate Student, Department of Plant Pathology and Microbiology Kevin Ong, Professor and Extension Plant Pathologist* Bacterial leaf spots occur worldwide and are usually caused by the bacteria Pseudomonas syringe and Xan- thomonas campestris, which can infect a wide range of host plants. Many plants in the Rosacea family, such as strawberry, Indian hawthorn, and peaches, are affected by bacterial leaf spots. Xanthomonas leaf spot of roses is a relatively new disease, first observed in Florida and Texas between 2004 and 2010. It has the potential to cause significant economic losses in commercial rose production. Cause The bacteria that cause the disease, members of the genus Xanthomonas, are tiny microorganisms that can move short distances in water with the help of a single Figure 2. As the infection worsens, the spots merge, causing necrosis flagellum, a hair-like structure that acts as a propeller. (death) on the leaf. A water-soaked appearance on infected leaves is also common. Source: Kevin Ong, Texas A&M AgriLife Extension Service Symptoms Xanthomonas leaf spot may look different form on the stems. In roses, chlorotic (yellowed) halos in various host plants, (Fig. 1) typically surround the small, brown, angular to but some of the most circular spots on the leaves. As the disease progresses common symptoms and the bacteria grows, the spots enlarge (Fig. 2). include the formation of spots between leaf veins Disease Movement (the centers of which The pathogen’s primary mode of transmission is may become necrotic splashing water, which allows it to spread to and infect and fall out) and a new leaves.
    [Show full text]
  • CRISPR Foki Dead Cas9 System: Principles and Applications in Genome Engineering
    cells Review CRISPR FokI Dead Cas9 System: Principles and Applications in Genome Engineering Maryam Saifaldeen y, Dana E. Al-Ansari y , Dindial Ramotar * and Mustapha Aouida * College of Health and Life Sciences, Division of Biological and Biomedical Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, Doha P.O.Box 34110, Qatar; [email protected] (M.S.); [email protected] (D.E.A.-A.) * Correspondence: [email protected] (D.R.); [email protected] (M.A.) These authors contributed equally to this work. y Received: 27 September 2020; Accepted: 19 November 2020; Published: 21 November 2020 Abstract: The identification of the robust clustered regularly interspersed short palindromic repeats (CRISPR) associated endonuclease (Cas9) system gene-editing tool has opened up a wide range of potential therapeutic applications that were restricted by more complex tools, including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Nevertheless, the high frequency of CRISPR system off-target activity still limits its applications, and, thus, advanced strategies for highly specific CRISPR/Cas9-mediated genome editing are continuously under development including CRISPR–FokI dead Cas9 (fdCas9). fdCas9 system is derived from linking a FokI endonuclease catalytic domain to an inactive Cas9 protein and requires a pair of guide sgRNAs that bind to the sense and antisense strands of the DNA in a protospacer adjacent motif (PAM)-out orientation, with a defined spacer sequence range around the target site. The dimerization of FokI domains generates DNA double-strand breaks, which activates the DNA repair machinery and results in genomic edit. So far, all the engineered fdCas9 variants have shown promising gene-editing activities in human cells when compared to other platforms.
    [Show full text]
  • TAL Effectors Are Remote Controls for Gene Activation Heidi Scholze and Jens Boch
    Available online at www.sciencedirect.com TAL effectors are remote controls for gene activation Heidi Scholze and Jens Boch TAL (transcription activator-like) effectors constitute a novel typically 34 amino acids (aa) long, but also repeat types of class of DNA-binding proteins with predictable specificity. They 30–42 aa can be found ([2], Figure 2). The last repeat is are employed by Gram-negative plant-pathogenic bacteria of only a half repeat. Repeat-to-repeat variations are limited the genus Xanthomonas which translocate a cocktail of to a few aa positions including two hypervariable residues different effector proteins via a type III secretion system (T3SS) at positions 12 and 13 per repeat. Typically, TALs differ into plant cells where they serve as virulence determinants. in their number of repeats while most contain 15.5–19.5 Inside the plant cell, TALs localize to the nucleus, bind to target repeats [2]. The repeat domain determines the specificity promoters, and induce expression of plant genes. DNA-binding of TALs which is mediated by selective DNA binding specificity of TALs is determined by a central domain of tandem [7,8]. TAL repeats constitute a novel type of DNA- repeats. Each repeat confers recognition of one base pair (bp) binding domain [7] distinct from classical zinc finger, in the DNA. Rearrangement of repeat modules allows design of helix–turn–helix, and leucine zipper motifs. proteins with desired DNA-binding specificities. Here, we summarize how TAL specificity is encoded, first structural data The recent understanding of the DNA-recognition speci- and first data on site-specific TAL nucleases.
    [Show full text]
  • E3 Ubiquitin Ligase SYVN1 Is a Key Positive Regulator for GSDMD
    bioRxiv preprint doi: https://doi.org/10.1101/2021.07.21.453219; this version posted July 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 E3 ubiquitin ligase SYVN1 is a key positive regulator for 2 GSDMD-mediated pyroptosis 3 4 Yuhua Shi 1,2,#, Yang Yang3,#, Weilv Xu1,#, Wei Xu1, Xinyu Fu1, Qian Lv1, Jie Xia1, 5 Fushan Shi1,2,* 6 1 Department of Veterinary Medicine, College of Animal Sciences, Zhejiang 7 University, Hangzhou 310058, Zhejiang, PR China 8 2 Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Zhejiang 9 University, Hangzhou 310058, Zhejiang, PR China 10 3 Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of 11 Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health 12 Inspection & Internet Technology, College of Animal Science and Technology & 13 College of Veterinary Medicine of Zhejiang A&F University, Hangzhou 311300, 14 Zhejiang, China 15 # These authors contributed equally to this work 16 *Corresponding author: Fushan Shi, E-mail: [email protected], Tel: 17 +086-0571-88982275 18 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.07.21.453219; this version posted July 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 19 Abstract 20 Gasdermin D (GSDMD) participates in activation of inflammasomes and pyroptosis. 21 Meanwhile, ubiquitination strictly regulates inflammatory responses. However, how 22 ubiquitination regulates Gasdermin D activity is not well understood.
    [Show full text]
  • A Single Plant Resistance Gene Promoter Engineered to Recognize Multiple TAL Effectors from Disparate Pathogens
    A single plant resistance gene promoter engineered to recognize multiple TAL effectors from disparate pathogens Patrick Ro¨ mer, Sabine Recht, and Thomas Lahaye1 Institute of Biology, Department of Genetics, Martin-Luther-University Halle-Wittenberg, D-06099 Halle (Saale), Germany Edited by Jeffery L. Dangl, University of North Carolina, Chapel Hill, NC, and approved October 2, 2009 (received for review August 6, 2009) Plant pathogenic bacteria of the genus Xanthomonas inject tran- factor UPA20, which induces hypertrophy (i.e., enlargement) of scription-activator like (TAL) effector proteins that manipulate the mesophyll cells, as well as to the promoters of other host genes hosts’ transcriptome to promote disease. However, in some cases that appear to contribute to susceptibility (14). In addition, plants take advantage of this mechanism to trigger defense re- AvrBs3 triggers a programmed cell death response, referred to sponses. For example, transcription of the pepper Bs3 and rice Xa27 as the hypersensitive response (HR), in pepper plants that resistance (R) genes are specifically activated by the respective TAL contain the cognate R gene Bs3 (15, 16). Certain pepper lines effectors AvrBs3 from Xanthomonas campestris pv. vesicatoria have an allele of Bs3 known as Bs3-E, which confers resistance (Xcv), and AvrXa27 from X. oryzae pv. oryzae (Xoo). Recognition of to strains carrying the AvrBs3 derivative AvrBs3⌬rep16 that has AvrBs3 was shown to be mediated by interaction with the corre- a deletion of repeat units 11–14 (15, 17). AvrBs3 and sponding UPT (UPregulated by TAL effectors) box UPTAvrBs3 present AvrBs3⌬rep16 were found to interact specifically with distinct in the promoter R gene Bs3 from the dicot pepper.
    [Show full text]
  • SNX8 Modulates Innate Immune Response to DNA Virus by Mediating Trafficking and Activation of MITA
    RESEARCH ARTICLE SNX8 modulates innate immune response to DNA virus by mediating trafficking and activation of MITA Jin Wei1³, Huan Lian1³, Wei Guo1, Yun-Da Chen1,2, Xia-Nan Zhang1,2, Ru Zang1, Li Zhong1, 1 1 3 1,2 1 Qing Yang , Ming-Ming Hu , Wei-Wei Luo , Hong-Bing Shu *, Shu LiID * 1 Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China, 2 College of Life Sciences, Wuhan University, Wuhan, China, 3 Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China a1111111111 a1111111111 ³ These authors share first authorship on this work. a1111111111 * [email protected] (HBS); [email protected] (SL) a1111111111 a1111111111 Abstract MITA (also called STING) is a central adaptor protein in innate immune response to cyto- solic DNA. Cellular trafficking of MITA from the ER to perinuclear microsomes after DNA OPEN ACCESS virus infection is critical for MITA activation and onset of innate antiviral response. Here we Citation: Wei J, Lian H, Guo W, Chen Y-D, Zhang found that SNX8 is a component of DNA-triggered induction of downstream effector genes X-N, Zang R, et al. (2018) SNX8 modulates innate and innate immune response. Snx8-/- mice infected with the DNA virus HSV-1 exhibited immune response to DNA virus by mediating trafficking and activation of MITA. PLoS Pathog 14 lower serum cytokine levels and higher viral titers in the brains, resulting in higher lethality. (10): e1007336. https://doi.org/10.1371/journal. Mechanistically, SNX8 recruited the class III phosphatylinositol 3-kinase VPS34 to MITA, ppat.1007336 which is required for trafficking of MITA from the ER to perinuclear microsomes.
    [Show full text]