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


Hepatitis B virus (HBV) represents a major risk factor for the development of hepatocarcinoma. Within the nucleus, HBV transcription is activated by both cellular and viral factors but is also repressed by cellular proteins that could be part of cellular antiviral defense mechanisms. Recently it has been shown that the regulatory protein HBx is essential to initiate and maintain HBV transcription in the setting of infection. Here we identify Spindlin1, a cellular protein involved in transcriptional regulation, as an HBx interacting partner. We show that Spindlin1 is recruited to the HBV DNA and inhibits its transcription in the context of infection. A virus deficient for the expression of HBx is more severely repressed by Spindlin1 than the wild type virus, suggesting that HBx counteracts Spindlin1 repression. We found that Spindlin1 also represses the transcription of Herpes Simplex Virus type 1 in the setting of infection. Our study not only provides new insights into the mechanisms regulating HBV transcription and the role of HBx in this process, but also reveals a new function of Spindlin1 as a component of the intrinsic antiviral defense.


Vyšlo v časopise: The Tudor Domain Protein Spindlin1 Is Involved in Intrinsic Antiviral Defense against Incoming Hepatitis B Virus and Herpes Simplex Virus Type 1. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004343
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004343

Souhrn

Hepatitis B virus (HBV) represents a major risk factor for the development of hepatocarcinoma. Within the nucleus, HBV transcription is activated by both cellular and viral factors but is also repressed by cellular proteins that could be part of cellular antiviral defense mechanisms. Recently it has been shown that the regulatory protein HBx is essential to initiate and maintain HBV transcription in the setting of infection. Here we identify Spindlin1, a cellular protein involved in transcriptional regulation, as an HBx interacting partner. We show that Spindlin1 is recruited to the HBV DNA and inhibits its transcription in the context of infection. A virus deficient for the expression of HBx is more severely repressed by Spindlin1 than the wild type virus, suggesting that HBx counteracts Spindlin1 repression. We found that Spindlin1 also represses the transcription of Herpes Simplex Virus type 1 in the setting of infection. Our study not only provides new insights into the mechanisms regulating HBV transcription and the role of HBx in this process, but also reveals a new function of Spindlin1 as a component of the intrinsic antiviral defense.


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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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