SUMO pathway dependent recruitment of cellular repressors to herpes simplex virus type 1 genomes
| Autor: | Amanda Sykes, Jill Murray, Kyle Grant, Anne Orr, Vera Lukashchuk, Delphine Cuchet-Lourenço, Chris Boutell, Roger D. Everett |
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| Rok vydání: | 2011 |
| Předmět: |
QH301-705.5
viruses Ubiquitin-Protein Ligases Mechanisms of Resistance and Susceptibility Immunology Amino Acid Motifs SUMO-1 Protein SUMO protein Genome Viral Biology Promyelocytic Leukemia Protein medicine.disease_cause Autoantigens Microbiology Virus Virology Molecular Cell Biology Genetics medicine Humans Simplexvirus Nuclear protein Biology (General) Molecular Biology Transcription factor Regulation of gene expression Cell Nucleus Tumor Suppressor Proteins Wild type Nuclear Proteins Sumoylation Antigens Nuclear Herpes Simplex RC581-607 Protein Inhibitors of Activated STAT Viral Replication Cellular Structures Ubiquitin ligase Repressor Proteins Herpes simplex virus HEK293 Cells DNA Viral biology.protein Parasitology Immunologic diseases. Allergy Transcription Factors Research Article |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 7, Iss 7, p e1002123 (2011) |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | Components of promyelocytic leukaemia (PML) nuclear bodies (ND10) are recruited to sites associated with herpes simplex virus type 1 (HSV-1) genomes soon after they enter the nucleus. This cellular response is linked to intrinsic antiviral resistance and is counteracted by viral regulatory protein ICP0. We report that the SUMO interaction motifs of PML, Sp100 and hDaxx are required for recruitment of these repressive proteins to HSV-1 induced foci, which also contain SUMO conjugates and PIAS2β, a SUMO E3 ligase. SUMO modification of PML and elements of its tripartite motif (TRIM) are also required for recruitment in cells lacking endogenous PML. Mutants of PML isoform I and hDaxx that are not recruited to virus induced foci are unable to reproduce the repression of ICP0 null mutant HSV-1 infection mediated by their wild type counterparts. We conclude that recruitment of ND10 components to sites associated with HSV-1 genomes reflects a cellular defence against invading pathogen DNA that is regulated through the SUMO modification pathway. Author Summary Viruses encounter several different defences that impede infection, including acquired immunity mediated by the immune system and innate immunity that includes the synthesis of antiviral proteins through the interferon pathway. In recent years, a third arm of antiviral defence has been described, named intrinsic immunity or intrinsic resistance, that is conferred by constitutively expressed cellular proteins. In the case of herpesviruses, intrinsic resistance involves the action of cellular repressors that restrict viral transcription once the viral genome enters the nucleus. Several studies have presented evidence that one aspect of intrinsic resistance involves cellular proteins that form distinct nuclear structures known as ND10. Several ND10 components are known to accumulate rapidly at sites in close association with herpes simplex virus type 1 genomes. Here we report that this cellular response requires the ability of several of the proteins in question to interact with a small ubiquitin-like protein known as SUMO. In two such examples of these proteins, we show that their ability to interact with SUMO is required for their roles in repressing viral infection. We suggest that this SUMO-dependent pathway may underlie a more general mechanism by which cells protect themselves from invading foreign DNA. |
| Databáze: | OpenAIRE |
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