| http://purl.uniprot.org/citations/28424288 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28424288 | http://www.w3.org/2000/01/rdf-schema#comment | "Viral protein R (Vpr) is an HIV-1 accessory protein whose function remains poorly understood. In this report, we sought to determine the requirement of Vpr for facilitating HIV-1 infection of monocyte-derived dendritic cells (MDDCs), one of the first cell types to encounter virus in the peripheral mucosal tissues. In this report, we characterize a significant restriction of Vpr-deficient virus replication and spread in MDDCs alone and in cell-to-cell spread in MDDC-CD4+ T cell cocultures. This restriction of HIV-1 replication in MDDCs was observed in a single round of virus replication and was rescued by the expression of Vpr in trans in the incoming virion. Interestingly, infections of MDDCs with viruses that encode Vpr mutants unable to interact with either the DCAF1/DDB1 E3 ubiquitin ligase complex or a host factor hypothesized to be targeted for degradation by Vpr also displayed a significant replication defect. While the extent of proviral integration in HIV-1-infected MDDCs was unaffected by the absence of Vpr, the transcriptional activity of the viral long terminal repeat (LTR) from Vpr-deficient proviruses was significantly reduced. Together, these results characterize a novel postintegration restriction of HIV-1 replication in MDDCs and show that the interaction of Vpr with the DCAF1/DDB1 E3 ubiquitin ligase complex and the yet-to-be-identified host factor might alleviate this restriction by inducing transcription from the viral LTR. Taken together, these findings identify a robust in vitro cell culture system that is amenable to addressing mechanisms underlying Vpr-mediated enhancement of HIV-1 replication.IMPORTANCE Despite decades of work, the function of the HIV-1 protein Vpr remains poorly understood, primarily due to the lack of an in vitro cell culture system that demonstrates a deficit in replication upon infection with viruses in the absence of Vpr. In this report, we describe a novel cell infection system that utilizes primary human dendritic cells, which display a robust decrease in viral replication upon infection with Vpr-deficient HIV-1. We show that this replication difference occurs in a single round of infection and is due to decreased transcriptional output from the integrated viral genome. Viral transcription could be rescued by virion-associated Vpr. Using mutational analysis, we show that domains of Vpr involved in binding to the DCAF1/DDB1/E3 ubiquitin ligase complex and prevention of cell cycle progression into mitosis are required for LTR-mediated viral expression, suggesting that the evolutionarily conserved G2 cell cycle arrest function of Vpr is essential for HIV-1 replication."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.org/dc/terms/identifier | "doi:10.1128/jvi.00051-17"xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/author | "Miller C.M."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/author | "Akiyama H."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/author | "Henderson A.J."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/author | "Emery A."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/author | "Swanstrom R.I."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/author | "Agosto L.M."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/author | "Gummuluru S."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/author | "Ettinger C.R."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/name | "J Virol"xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/pages | "e00051-17"xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/title | "Virion-Associated Vpr Alleviates a Postintegration Block to HIV-1 Infection of Dendritic Cells."xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://purl.uniprot.org/core/volume | "91"xsd:string |
| http://purl.uniprot.org/citations/28424288 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28424288 |
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