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Title
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Y-box-binding protein 1 supports the early and late steps of HIV replication
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Author
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Abstract
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| The human immunodeficiency virus (HIV) depends on cellular proteins, so-called cofactors, to complete its replication cycle. In search for new therapeutic targets we identified the DNA and RNA binding protein Y-box-binding Protein 1 (YB-1) as a cofactor supporting early and late steps of HIV replication. YB-1 depletion resulted in a 10-fold decrease in HIV-1 replication in different cell lines. Dissection of the replication defects revealed that knockdown of YB-1 is associated with a 2- to 5-fold decrease in virion production due to interference with the viral RNA metabolism. Using single-round virus infection experiments we demonstrated that early HIV-1 replication also depends on the cellular YB-1 levels. More precisely, using quantitative PCR and an in vivo nuclear import assay with fluorescently labeled viral particles, we showed that YB-1 knockdown leads to a block between reverse transcription and nuclear import of HIV-1. Interaction studies revealed that YB-1 associates with integrase, although a direct interaction with HIV integrase could not be unambiguously proven. In conclusion, our results indicate that YB-1 affects multiple stages of HIV replication. Future research on the interaction between YB-1 and the virus will reveal whether this protein qualifies as a new antiviral target. |
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Language
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English
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Source (journal)
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PLoS ONE
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Publication
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2018
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ISSN
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1932-6203
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DOI
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10.1371/JOURNAL.PONE.0200080
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Volume/pages
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13
:7
(2018)
, 24 p.
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Article Reference
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e0200080
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ISI
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000438388800041
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Pubmed ID
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29995936
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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