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Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity.

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  • معلومة اضافية
    • Publication Information:
      Public Library of Science (PLoS), 2019.
    • Publication Date:
      2019
    • Collection:
      DOAJ-Articles_enriched
      DOAJ-Articles
    • Abstract:
      Natural variation separates Epstein-Barr virus (EBV) into type 1 and type 2 strains. Type 2 EBV is less transforming in vitro due to sequence differences in the EBV transcription factor EBNA2. This correlates with reduced activation of the EBV oncogene LMP1 and some cell genes. Transcriptional activation by type 1 EBNA2 can be suppressed through the binding of two PXLXP motifs in its transactivation domain (TAD) to the dimeric coiled-coil MYND domain (CC-MYND) of the BS69 repressor protein (ZMYND11). We identified a third conserved PXLXP motif in type 2 EBNA2. We found that type 2 EBNA2 peptides containing this motif bound BS69CC-MYND efficiently and that the type 2 EBNA2TAD bound an additional BS69CC-MYND molecule. Full-length type 2 EBNA2 also bound BS69 more efficiently in pull-down assays. Molecular weight analysis and low-resolution structures obtained using small-angle X-ray scattering showed that three BS69CC-MYND dimers bound two molecules of type 2 EBNA2TAD, in line with the dimeric state of full-length EBNA2 in vivo. Importantly, mutation of the third BS69 binding motif in type 2 EBNA2 improved B-cell growth maintenance and the transcriptional activation of the LMP1 and CXCR7 genes. Our data indicate that increased association with BS69 restricts the function of type 2 EBNA2 as a transcriptional activator and driver of B cell growth and may contribute to reduced B-cell transformation by type 2 EBV.
    • Accession Number:
      pmc: PMC6638984
      pmid: 31283782
    • ISSN:
      1553-7374
      1553-7366
    • Accession Number:
      10.1371/journal.ppat.1007458
    • Accession Number:
      edsair.dedup.wf.001..cddb67b2d46186a8ca7357be475a4d4d
  • Citations
    • ABNT:
      MANCINI, E. J. et al. Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity. PLoS Pathogens, [s. l.], v. 15, 2019. DOI 10.1371/journal.ppat.1007458. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsair&AN=edsair.dedup.wf.001..cddb67b2d46186a8ca7357be475a4d4d&custid=s8280428. Acesso em: 28 maio. 2020.
    • AMA:
      Mancini EJ, West MJ, Ponnusamy R, et al. Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity. PLoS Pathogens. 2019;15. doi:10.1371/journal.ppat.1007458.
    • APA:
      Mancini, E. J., West, M. J., Ponnusamy, R., Khatri, R., Correia, P. B., Wood, C. D., & Farrell, P. J. (2019). Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity. PLoS Pathogens, 15. https://doi.org/10.1371/journal.ppat.1007458
    • Chicago/Turabian: Author-Date:
      Mancini, Erika J., Michelle J. West, Rajesh Ponnusamy, Ritika Khatri, Paulo B. Correia, C. David Wood, and Paul J. Farrell. 2019. “Increased Association between Epstein-Barr Virus EBNA2 from Type 2 Strains and the Transcriptional Repressor BS69 Restricts EBNA2 Activity.” PLoS Pathogens 15 (July). doi:10.1371/journal.ppat.1007458.
    • Harvard:
      Mancini, E. J. et al. (2019) ‘Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity’, PLoS Pathogens, 15. doi: 10.1371/journal.ppat.1007458.
    • Harvard: Australian:
      Mancini, EJ, West, MJ, Ponnusamy, R, Khatri, R, Correia, PB, Wood, CD & Farrell, PJ 2019, ‘Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity’, PLoS Pathogens, vol. 15, viewed 28 May 2020, .
    • MLA:
      Mancini, Erika J., et al. “Increased Association between Epstein-Barr Virus EBNA2 from Type 2 Strains and the Transcriptional Repressor BS69 Restricts EBNA2 Activity.” PLoS Pathogens, vol. 15, July 2019. EBSCOhost, doi:10.1371/journal.ppat.1007458.
    • Chicago/Turabian: Humanities:
      Mancini, Erika J., Michelle J. West, Rajesh Ponnusamy, Ritika Khatri, Paulo B. Correia, C. David Wood, and Paul J. Farrell. “Increased Association between Epstein-Barr Virus EBNA2 from Type 2 Strains and the Transcriptional Repressor BS69 Restricts EBNA2 Activity.” PLoS Pathogens 15 (July 1, 2019). doi:10.1371/journal.ppat.1007458.
    • Vancouver/ICMJE:
      Mancini EJ, West MJ, Ponnusamy R, Khatri R, Correia PB, Wood CD, et al. Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity. PLoS Pathogens [Internet]. 2019 Jul 1 [cited 2020 May 28];15. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsair&AN=edsair.dedup.wf.001..cddb67b2d46186a8ca7357be475a4d4d&custid=s8280428