SUMO Pathway Dependent Recruitment of Cellular Repressors to Herpes Simplex Virus Type 1 Genomes

PLoS Pathogens

Delphine Cuchet-Lourenço¹  Amanda Sykes¹  Roger D. Everett¹  Vera Lukashchuk¹  Kyle Grant¹  Jill Murray¹  Chris Boutell¹  Anne Orr¹ 

[1] MRC-University of Glasgow Centre for Virus Research, Glasgow, Scotland, United Kingdom

关键词: SUMOylation;    Lysine;    Antimicrobial resistance;    Viral genome;    Viral structure;    Herpes simplex virus-1;    Viral genomics;    Comparative genomics;   

DOI  :  10.1371/journal.ppat.1002123

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY