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Basic Characteristics of Mutations
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Mutation Site
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P90A |
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Mutation Site Sentence
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With the exception of TNPO1, which has been previously shown to bind P90A CA [23], these were almost absent from the pellet in cells infected with the P90A capsid mutant (Figure 4A). |
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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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CA |
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Standardized Encoding Gene
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Gag
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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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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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capsid |
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Location
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- |
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Literature Information
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PMID
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32545337
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Title
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Daxx Inhibits HIV-1 Reverse Transcription and Uncoating in a SUMO-Dependent Manner
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Author
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Maillet S,Fernandez J,Decourcelle M,El Koulali K,Blanchet FP,Arhel NJ,Maarifi G,Nisole S
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Journal
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Viruses
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Journal Info
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2020 Jun 11;12(6):636
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Abstract
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Death domain-associated protein 6 (Daxx) is a multifunctional, ubiquitously expressed and highly conserved chaperone protein involved in numerous cellular processes, including apoptosis, transcriptional repression, and carcinogenesis. In 2015, we identified Daxx as an antiretroviral factor that interfered with HIV-1 replication by inhibiting the reverse transcription step. In the present study, we sought to unravel the molecular mechanism of Daxx-mediated restriction and, in particular, to identify the protein(s) that Daxx targets in order to achieve its antiviral activity. First, we show that the SUMO-interacting motif (SIM) located at the C-terminus of the protein is strictly required for Daxx to inhibit HIV-1 reverse transcription. By performing a quantitative proteomic screen combined with classical biochemical analyses, we found that Daxx associated with incoming HIV-1 cores through a SIM-dependent interaction with cyclophilin A (CypA) and capsid (CA). Daxx was found to reside within a multiprotein complex associated with viral capsids, also containing TNPO3, TRIM5alpha, and TRIM34. Given the well-known influence of these cellular factors on the stability of HIV-1 cores, we investigated the effect of Daxx on the cytoplasmic fate of incoming cores and found that Daxx prevented HIV-1 uncoating in a SIM-dependent manner. Altogether, our findings suggest that, by recruiting TNPO3, TRIM5alpha, and TRIM34 and possibly other proteins onto incoming HIV-1 cores through a SIM-dependent interaction with CA-bound CypA, Daxx increases their stability, thus preventing uncoating and reverse transcription. Our study uncovers a previously unknown function of Daxx in the early steps of HIV-1 infection and further illustrates how reverse transcription and uncoating are two tightly interdependent processes.
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Sequence Data
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-
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