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Y-box-binding protein 1 supports the early and late steps of HIV replication.
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- المؤلفون: Weydert, Caroline1; van Heertum, Bart1; Dirix, Lieve1,2; De Houwer, Stéphanie1; De Wit, Flore1; Mast, Jan3; Husson, Steven J.4,5; Busschots, Katrien1; König, Renate6; Gijsbers, Rik1; De Rijck, Jan1; Debyser, Zeger1
- المصدر:
PLoS ONE. 7/11/2018, Vol. 13 Issue 7, p1-24. 24p.
- الموضوع:
- معلومة اضافية
- نبذة مختصرة :
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. [ABSTRACT FROM AUTHOR]
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