Title
|
|
|
|
Y-box-binding protein 1 supports the early and late steps of HIV replication
| |
Author
|
|
|
|
| |
Abstract
|
|
|
|
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. |
| |
Language
|
|
|
|
English
| |
Source (journal)
|
|
|
|
PLoS ONE
| |
Publication
|
|
|
|
2018
| |
ISSN
|
|
|
|
1932-6203
| |
DOI
|
|
|
|
10.1371/JOURNAL.PONE.0200080
| |
Volume/pages
|
|
|
|
13
:7
(2018)
, 24 p.
| |
Article Reference
|
|
|
|
e0200080
| |
ISI
|
|
|
|
000438388800041
| |
Pubmed ID
|
|
|
|
29995936
| |
Medium
|
|
|
|
E-only publicatie
| |
Full text (Publisher's DOI)
|
|
|
|
| |
Full text (open access)
|
|
|
|
| |
|