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Epstein–Barr virus nuclear antigen (EBNA) 3A induces the expression of and interacts with a subset of chaperones and co-chaperones
- Source :
- The Journal of General Virology
- Publication Year :
- 2008
- Publisher :
- Microbiology Society, 2008.
-
Abstract
- Viral nuclear oncoproteins EBNA3A and EBNA3C are essential for the efficient immortalization of B cells by Epstein–Barr virus (EBV) in vitro and it is assumed that they play an essential role in viral persistence in the human host. In order to identify cellular genes regulated by EBNA3A expression, cDNA encoding EBNA3A was incorporated into a recombinant adenoviral vector. Microarray analysis of human diploid fibroblasts infected with either adenovirus EBNA3A or an empty control adenovirus consistently showed an EBNA3A-specific induction of mRNA corresponding to the chaperones Hsp70 and Hsp70B/B′ and co-chaperones Bag3 and DNAJA1/Hsp40. Analysis of infected fibroblasts by real-time quantitative RT-PCR and Western blotting confirmed that EBNA3A, but not EBNA3C, induced expression of Hsp70, Hsp70B/B′, Bag3 and DNAJA1/Hsp40. This was also confirmed in a stable, inducible expression system. EBNA3A activated transcription from the Hsp70B promoter, but not multimerized heat-shock elements in transient transfection assays, consistent with specific chaperone and co-chaperone upregulation. Co-immunoprecipitation experiments suggest that EBNA3A can form a complex with the chaperone/co-chaperone proteins in both adenovirus-infected cells and EBV-immortalized lymphoblastoid cell lines. Consistent with this, induction of EBNA3A resulted in redistribution of Hsp70 from the cytoplasm to the nucleus. EBNA3A therefore specifically induces (and then interacts with) all of the factors necessary for an active Hsp70 chaperone complex.
- Subjects :
- Transcriptional Activation
Active Transport, Cell Nucleus
HSP72 Heat-Shock Proteins
Biology
BAG3
medicine.disease_cause
Virus
Cell Line
Viral vector
03 medical and health sciences
0302 clinical medicine
Virology
medicine
Humans
HSP70 Heat-Shock Proteins
Promoter Regions, Genetic
Adaptor Proteins, Signal Transducing
030304 developmental biology
Cell Nucleus
0303 health sciences
Animal
Microarray analysis techniques
HSP40 Heat-Shock Proteins
Cell Transformation, Viral
Molecular biology
Epstein–Barr virus
Up-Regulation
3. Good health
Epstein-Barr Virus Nuclear Antigens
Cytoplasm
030220 oncology & carcinogenesis
Chaperone (protein)
biology.protein
Chaperone complex
Apoptosis Regulatory Proteins
Subjects
Details
- ISSN :
- 14652099 and 00221317
- Volume :
- 89
- Database :
- OpenAIRE
- Journal :
- Journal of General Virology
- Accession number :
- edsair.doi.dedup.....2015354d6943fa782e12a509c8254751