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

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2014 Sep 12

PMID 25211330

Citations 27

Authors

Aurelie Ducroux

Shirine Benhenda

Lise Riviere

O John Semmes

Monsef Benkirane

Christine Neuveut

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome.

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