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Abstract
The promyelocytic leukemia protein (PML) is the main structural component of the nuclear matrix structures termed nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs). PML and ND10 structures have been shown to mediate an intrinsic immune response against a variety of different viruses. Their role during retroviral replication, however, is still controversially discussed. In this study, we analyzed the role of PML and the ND10 components Daxx and Sp100 during retroviral replication in different cell types. Using cell lines exhibiting a shRNA-mediated knockdown, we found that PML, but not Daxx or Sp100, inhibits HIV and other retroviruses in a cell type-dependent manner. The PML-mediated block to retroviral infection was active in primary human fibroblasts and murine embryonic fibroblasts but absent from T cells and myeloid cell lines. Quantitative PCR analysis of HIV cDNA in infected cells revealed that PML restricts infection at the level of reverse transcription. Our findings shed light on the controversial role of PML during retroviral infection and show that PML contributes to the intrinsic restriction of retroviral infections in a cell type-dependent manner.
Highlights
The promyelocytic leukemia protein (PML/TRIM19) is a member of the tripartite motif (TRIM)protein family and contains an amino-terminal TRIM motif consisting of a RING domain, twoB-Boxes and a coiled coil domain [1,2]
In human foreskin fibroblast (HFF) shC cells, we found PML to be localized in nuclear speckles, the previously described nuclear domain 10 (ND10) structures (Figure 1B)
Compared to shRNA directed against PML (shPML) cells, we found that the infectivity of HIV-GFP was strongly reduced in shC cells independently of HIV accessory proteins
Summary
The promyelocytic leukemia protein (PML/TRIM19) is a member of the tripartite motif (TRIM)protein family and contains an amino-terminal TRIM motif consisting of a RING domain, twoB-Boxes and a coiled coil domain [1,2]. The promyelocytic leukemia protein (PML/TRIM19) is a member of the tripartite motif (TRIM). Protein family and contains an amino-terminal TRIM motif consisting of a RING domain, two. Seven different PML isoforms have been described, all of which contain a TRIM motif but differ within their carboxyterminal sequences due to differential splicing. The PML isoforms I through VI are located in the nucleus of the cell, whereas isoform. PML is the major organizing component of nuclear domain 10 (ND10) structures. Within ND10, PML is modified by binding to the small ubiquitin-like modifier (SUMO), which leads to the stabilization of the ND10 structures and the recruitment of the permanently ND10-associated proteins Daxx and Sp100, as well as many other transiently associated proteins depending on exogenous influences and cellular conditions [3,4]. PML and ND10 structures have been implicated in a variety of different functions, Viruses 2016, 8, 2; doi:10.3390/v8010002 www.mdpi.com/journal/viruses
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