Journal Article

Y-box-binding protein 1 supports the early and late steps of HIV replication

van Heertum, Bart, De Wit, Flore, Busschots, Katrien, König, Renate, Debyser, Zeger, Husson, Steven J., Dirix, Lieve, Weydert, Caroline, De Houwer, Stéphanie, Gijsbers, Rik, De Rijck, Jan, Mast, Jan

2018

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology / Biology and Life Sciences / Cancer / Care and treatment / Cell lines / Cofactors / Deoxyribonucleic acid / Development and progression / DNA / Gene expression / Gene therapy / Genetic aspects / Genomes / Health aspects / HIV / HIV infections / Human immunodeficiency virus / Imports / Infections / Integrase / Kinases / Laboratories / Medicine and Health Sciences / Metabolism / Nuclear transport / Pharmaceuticals / Proteins / Replication / Research and Analysis Methods / Reverse transcription / Ribonucleic acid / RNA / RNA viruses / RNA-binding protein / RNA-mediated interference / Target recognition / Therapeutic applications / Transcription factors / Virions / Virology / Virus replication / Viruses