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Basic Characteristics of Mutations
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Mutation Site
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H71R |
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Mutation Site Sentence
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Indeed, two Vpr point mutants, which are unable to bind the ligase adaptor protein DCAF1, Q65R Vpr, and H71R Vpr, failed to increase unintegrated virus expression (Figure 1G) |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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Vpr |
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Standardized Encoding Gene
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Vpr
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Acquired Immunodeficiency Syndrome
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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Vpr |
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Location
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- |
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Literature Information
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PMID
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33811831
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Title
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The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr
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Author
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Dupont L,Bloor S,Williamson JC,Cuesta SM,Shah R,Teixeira-Silva A,Naamati A,Greenwood EJD,Sarafianos SG,Matheson NJ,Lehner PJ
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Journal
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Cell host & microbe
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Journal Info
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2021 May 12;29(5):792-805
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Abstract
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Silencing of nuclear DNA is an essential feature of innate immune responses to invading pathogens. Early in infection, unintegrated lentiviral cDNA accumulates in the nucleus yet remains poorly expressed. In HIV-1-like lentiviruses, the Vpr accessory protein enhances unintegrated viral DNA expression, suggesting Vpr antagonizes cellular restriction. We previously showed how Vpr remodels the host proteome, identifying multiple cellular targets. We now screen these using a targeted CRISPR-Cas9 library and identify SMC5-SMC6 complex localization factor 2 (SLF2) as the Vpr target responsible for silencing unintegrated HIV-1. SLF2 recruits the SMC5/6 complex to unintegrated lentiviruses, and depletion of SLF2, or the SMC5/6 complex, increases viral expression. ATAC-seq demonstrates that Vpr-mediated SLF2 depletion increases chromatin accessibility of unintegrated virus, suggesting that the SMC5/6 complex compacts viral chromatin to silence gene expression. This work implicates the SMC5/6 complex in nuclear immunosurveillance of extrachromosomal DNA and defines its targeting by Vpr as an evolutionarily conserved antagonism.
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Sequence Data
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-
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