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Basic Characteristics of Mutations
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Mutation Site
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W54R |
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Mutation Site Sentence
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To understand how Vpr could increase Env expression, we introduced 6 mutations into these regions of Vpr, which include A30L, F34I, W54R, Q65R, and H71R. |
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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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pNL4-3
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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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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- |
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Location
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- |
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Literature Information
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PMID
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27343732
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Title
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HIV-1 Vpr increases Env expression by preventing Env from endoplasmic reticulum-associated protein degradation (ERAD)
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Author
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Zhang X,Zhou T,Frabutt DA,Zheng YH
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Journal
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Virology
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Journal Info
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2016 Sep;496:194-202
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Abstract
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Vpr enhances HIV-1 replication in macrophages and dendritic cells, as well as the human CD4(+) CEM.NKR T cell line. Recently, Vpr was reported to increase HIV-1 Env expression in macrophages. Here, we report that Vpr also increases HIV-1 Env expression in dendritic cells and CEM.NKR cells. The Vpr activity depends on its N-terminal region, which was disrupted by a single A30L mutation. Env was rapidly degraded in the absence of Vpr, which was blocked by the ERAD pathway inhibitor kifunesine or the lysosome inhibitor Bafilomycin. As2O3 or PK11195, which reportedly enhances HIV-1 Env folding, also blocked the Env degradation in CEM.NKR cells. Thus, these results not only identify Env as a primary target for Vpr to boost HIV-1 replication, but also suggest that Vpr likely promotes Env folding in the ER, which is otherwise misfolded and targeted by the ERAD pathway to lysosomes for degradation.
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Sequence Data
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-
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