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http://purl.uniprot.org/citations/27000403http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27000403http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27000403http://www.w3.org/2000/01/rdf-schema#comment"

Background

The promyelocytic leukemia (PML) protein, a type I interferon (IFN-I)-induced gene product and a member of the tripartite motif (TRIM) family, modulates the transcriptional activity of viruses belonging to various families. Whether PML has an impact on the replication of HIV-1 has not been fully addressed, but recent studies point to its possible involvement in the restriction of HIV-1 in human cells and in the maintenance of transcriptional latency in human cell lines in which HIV-1 is constitutively repressed. We investigated further the restriction of HIV-1 and a related lentivirus, SIVmac, by PML in murine cells and in a lymphocytic human cell line. In particular, we studied the relevance of PML to IFN-I-mediated inhibition and the role of individual human isoforms.

Results

We demonstrate that both human PML (hPML) and murine PML (mPML) inhibit the early post-entry stages of the replication of HIV-1 and a related lentivirus, SIVmac. In addition, HIV-1 was transcriptionally silenced by mPML and by hPML isoforms I, II, IV and VI in MEFs. This PML-mediated transcriptional repression was attenuated in presence of the histone deacetylase inhibitor SAHA. In contrast, depletion of PML had no effect on HIV-1 gene expression in a human T cell line. PML was found to contribute to the inhibition of HIV-1 by IFN-I. Specifically, IFN-α and IFN-β treatments of MEFs enhanced the PML-dependent inhibition of HIV-1 early replication stages.

Conclusions

We show that PML can inhibit HIV-1 and other lentiviruses as part of the IFN-I-mediated response. The restriction takes place at two distinct steps, i.e. reverse transcription and transcription, and in an isoform-specific, cellular context-specific fashion. Our results support a model in which PML activates innate immune antilentiviral effectors. These data are relevant to the development of latency reversal-inducing pharmacological agents, since PML was previously proposed as a pharmacological target for such inhibitors. This study also has implications for the development of murine models of HIV-1."xsd:string
http://purl.uniprot.org/citations/27000403http://purl.org/dc/terms/identifier"doi:10.1186/s12977-016-0253-1"xsd:string
http://purl.uniprot.org/citations/27000403http://purl.org/dc/terms/identifier"doi:10.1186/s12977-016-0253-1"xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/author"Masroori N."xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/author"Masroori N."xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/author"Berthoux L."xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/author"Berthoux L."xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/author"Merindol N."xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/author"Merindol N."xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/name"Retrovirology"xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/name"Retrovirology"xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/pages"19"xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/pages"19"xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/title"The interferon-induced antiviral protein PML (TRIM19) promotes the restriction and transcriptional silencing of lentiviruses in a context-specific, isoform-specific fashion."xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/title"The interferon-induced antiviral protein PML (TRIM19) promotes the restriction and transcriptional silencing of lentiviruses in a context-specific, isoform-specific fashion."xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/volume"13"xsd:string
http://purl.uniprot.org/citations/27000403http://purl.uniprot.org/core/volume"13"xsd:string
http://purl.uniprot.org/citations/27000403http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27000403
http://purl.uniprot.org/citations/27000403http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27000403
http://purl.uniprot.org/citations/27000403http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27000403
http://purl.uniprot.org/citations/27000403http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27000403
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