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PML/TRIM19-Dependent Inhibition of Retroviral Reverse-Transcription by Daxx


Among the several protection mechanisms raised by mammalian organisms against viral infections, an early line of defense consists of cellular proteins known as restriction factors that interfere with viral replication. PML, also known as TRIM19, is one of these proteins and has been shown to inhibit diverse viruses. PML is mainly expressed in the nucleus, where it forms dynamic structures known as PML nuclear bodies that recruit many other proteins, such as Sp100 and Daxx. While the role of PML/TRIM19 in antiviral defense is well documented, its effect on HIV-1 infection remains unclear. Here we show that PML is rapidly re-localized in the cytoplasm of cells infected by HIV-1 and other retroviruses and interferes with reverse-transcription of incoming retroviral RNA. We were able to demonstrate that PML does not inhibit retroviral infection directly but through the stabilization of one of its well-characterized partners, Daxx. In the presence of PML, Daxx inhibits an early step of reverse-transcription thereby interfering with retroviral infections. Our findings unravel a novel antiviral function for PML and its partner Daxx.


Vyšlo v časopise: PML/TRIM19-Dependent Inhibition of Retroviral Reverse-Transcription by Daxx. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005280
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005280

Souhrn

Among the several protection mechanisms raised by mammalian organisms against viral infections, an early line of defense consists of cellular proteins known as restriction factors that interfere with viral replication. PML, also known as TRIM19, is one of these proteins and has been shown to inhibit diverse viruses. PML is mainly expressed in the nucleus, where it forms dynamic structures known as PML nuclear bodies that recruit many other proteins, such as Sp100 and Daxx. While the role of PML/TRIM19 in antiviral defense is well documented, its effect on HIV-1 infection remains unclear. Here we show that PML is rapidly re-localized in the cytoplasm of cells infected by HIV-1 and other retroviruses and interferes with reverse-transcription of incoming retroviral RNA. We were able to demonstrate that PML does not inhibit retroviral infection directly but through the stabilization of one of its well-characterized partners, Daxx. In the presence of PML, Daxx inhibits an early step of reverse-transcription thereby interfering with retroviral infections. Our findings unravel a novel antiviral function for PML and its partner Daxx.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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