Positive Role of Promyelocytic Leukemia Protein in Type I Interferon Response and Its Regulation by Human Cytomegalovirus

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For productive viral infection, virus needs to overcome successive host defenses including intrinsic defense and innate and acquired immunity. Promyelocytic leukemia protein (PML) has been shown to play an important role in intrinsic defense by acting as a nuclear restriction factor that suppresses incoming viral genomes. In this study, we demonstrate that PML also positively regulates type I interferon response by promoting transcription of interferon-stimulated genes (ISGs). Therefore, PML is a key player in both intrinsic and innate host defenses. We further show that this regulation by PML in type I interferon response is inhibited by human cytomegalovirus (HCMV) IE1 protein, which forms a complex with PML, STAT1, STAT2, and HDACs in virus-infected cells. By analyzing mutant viruses, we demonstrate that IE1 inhibits ISG transcription by sequestering interferon-stimulated gene factor 3 (ISGF3) in a manner requiring its binding of PML and STAT2, but not of HDACs. Our findings reveal that PML is a regulator of ISGF3 in type I interferon response and that this PML activity is counteracted by HCMV IE1. Our study explains why PML targeting activity is widely conserved among many viruses.

Vyšlo v časopise: Positive Role of Promyelocytic Leukemia Protein in Type I Interferon Response and Its Regulation by Human Cytomegalovirus. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004785
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004785

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