%0 Journal Article %J PLoS One %D 2018 %T Y-box-binding protein 1 supports the early and late steps of HIV replication. %A Weydert, Caroline %A Bart van Heertum %A Lieve Dirix %A Stéphanie De Houwer %A Flore De Wit %A Jan Mast %A Steven J Husson %A Katrien Busschots %A Renate König %A Gijsbers, Rik %A De Rijck, Jan %A Debyser, Zeger %X

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.

%B PLoS One %V 13 %8 2018 %G eng %N 7 %R 10.1371/journal.pone.0200080