YB-1 relocates to the nucleus in adenovirus-infected cells and facilitates viral replication by inducing E2 gene expression through the E2 late promoter.
The adenovirus early proteins E1A and E1B-55kDa are key regulators of viral DNA replication, and it was thought that targeting of p53 by E1B-55kDa is essential for this process. Here we have identified a previously unrecognized function of E1B for adenovirus replication. We found that E1B-55kDa is involved in targeting the transcription factor YB-1 to the nuclei of adenovirus type 5-infected cells where it is associated with viral inclusion bodies believed to be sites of viral transcription and replication. We show that YB-1 facilitates E2 gene expression through the E2 late promoter thus controlling E2 gene activity at later stages of infection. The role of YB-1 for adenovirus replication was demonstrated with an E1-minus adenovirus vector containing a YB-1 transgene. In infected cells, AdYB-1 efficiently replicated and produced infectious progeny particles. Thus, adenovirus E1B-55kDa protein and the host cell factor YB-1 act jointly to facilitate adenovirus replication in the late phase of infection.
Holm
Per S
PS
Institut für Experimentelle Onkologie und Therapieforschung, Technische Universität München, Klinikum Rechts der Isar, München 81675, Germany. per.s.holm@lrz.tum.de
Bergmann
Stephan
S
Jurchott
Karsten
K
Lage
Hermann
H
Brand
Karsten
K
Ladhoff
Axel
A
Mantwill
Klaus
K
Curiel
David T
DT
Dobbelstein
Matthias
M
Dietel
Manfred
M
Gansbacher
Bernd
B
Royer
Hans-Dieter
HD
D021581:Active Transport, Cell Nucleus; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D017502:Adenovirus E2 Proteins / Q000235:genetics*; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000378:metabolism; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors; D019076:Transgenes; D014779:Virus Replication; D051840:Y-Box-Binding Protein 1
D017502:Adenovirus E2 Proteins; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; C097324:P55-L5 protein, Borrelia burgdorferi; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human