The Tudor Domain Protein Spindlin1 Is Involved in Intrinsic Antiviral Defense against Incoming Hepatitis B Virus and Herpes Simplex Virus Type 1

PLoS Pathogens

Christine Neuveut¹  Shirine Benhenda¹  O. John Semmes¹  Lise Rivière²  Aurélie Ducroux²  Monsef Benkirane² 

[1] UMR CNRS 3569, Paris, France;Unité des Hépacivirus et Immunité Innée, Institut Pasteur, Paris, France

关键词: DNA transcription;    Immunoprecipitation;    Hepatitis B virus;    Transcriptional control;    DNA replication;    RNA extraction;    Chromatin;    Herpes simplex virus-1;   

DOI  :  10.1371/journal.ppat.1004343

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Hepatitis B virus infection (HBV) is a major risk factor for the development of hepatocellular carcinoma. HBV replicates from a covalently closed circular DNA (cccDNA) that remains as an episome within the nucleus of infected cells and serves as a template for the transcription of HBV RNAs. The regulatory protein HBx has been shown to be essential for cccDNA transcription in the context of infection. Here we identified Spindlin1, a cellular Tudor-domain protein, as an HBx interacting partner. We further demonstrated that Spindlin1 is recruited to the cccDNA and inhibits its transcription in the context of infection. Spindlin1 knockdown induced an increase in HBV transcription and in histone H4K4 trimethylation at the cccDNA, suggesting that Spindlin1 impacts on epigenetic regulation. Spindlin1-induced transcriptional inhibition was greater for the HBV virus deficient for the expression of HBx than for the HBV WT virus, suggesting that HBx counteracts Spindlin1 repression. Importantly, we showed that the repressive role of Spindlin1 is not limited to HBV transcription but also extends to other DNA virus that replicate within the nucleus such as Herpes Simplex Virus type 1 (HSV-1). Taken together our results identify Spindlin1 as a critical component of the intrinsic antiviral defense and shed new light on the function of HBx in HBV infection.

【 授权许可】

CC BY