ULB Center for Diabetes Research

Type 1 Diabetes and Viruses

Group Leader: Anne Op de beeck

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At the ULB, Dr Op de beeck joined her virologist expertise to the team of the laboratory of Decio Eizirik devoted to the study of type 1 diabetes (T1D), an autoimmune disease caused by a progressive immune-mediated loss of pancreatic β-cell mass via apoptosis.

 

Group Leader, Anne Op de beeck

Anne Op de beeck obtained her Master degree at the Université Libre de Bruxelles in 1989, and obtained a PhD degree at the Université Libre de Bruxelles in 1996. During her PhD she was the first to describe the cytostatic property of the parvoviral protein NS1 and to unravel the underlying mechanisms, paving the way in the emerging field of viral interference with the cell cycle. She further worked as a postdoctoral fellow in the laboratory of Jean Dubuisson at the Institut de Biologie de Lille/Institut Pasteur de Lille in France. Her post doc was devoted to the characterization of the process of assembly of the envelope of Hepatitis C and of Yellow Fever Viruses and to the study of the complex process of entry of hepatitis C virus. In 2004 she obtained a researcher permanent position at the Centre National de la Rercherche Scientifique (CNRS). She is currently detached from the CNRS and holds appointments as Chargée de Cours/Associate Professor of the Faculty of Medicine, Université Libre de Bruxelles.

 

Research Interests

At the ULB, Dr Op de beeck joined her virologist expertise to the team of the laboratory of Decio Eizirik devoted to the study of type 1 diabetes (T1D). T1D is an autoimmune disease caused by a progressive immune-mediated loss of pancreatic β-cell mass via apoptosis. The triggering of T1DM depends on environmental factors that interact with predisposing genes to induce the autoimmune assault against β-cells. Among the potential environmental factors, epidemiological, clinical and pathology studies in humans support the implication of viral infections, particularly by enteroviruses (for example, Coxsackievirus), as triggers for the development of T1DM. In line with this, many candidate genes for T1DM regulate antiviral responses in both β-cells and the immune system.

The principal research interests of the Op de beeck group are the characterization of virus induced beta cell death and dysfunction and the identification of factors involved in beta cell permissiveness to viral infection.

In collaboration with Eizirik, Op de beeck unveil the mechanism of Coxsackieviruses induced beta cell death, the powerful antiviral response of pancreatic alpha cells to viral infection and the key role played by IFN-alpha in the early steps of T1D. She also recently described that Coxsackievirus tailors the unfolded protein response to ER stress to favor viral amplification in panceratic beta cells.

Selected Publications

  1. M. Colli, F. Paula, M-L. Draps, L. Marselli, P. Marchetti, M. Roivainen, D.Eizirik, A. Op de beeck. Coxsackievirus B tailors the unfolded protein response to favour viral amplification in pancreatic beta cells. Submited
  2. D. Eizirik and A. Op de Beeck. Coxsackievirus and type 1 diabetes – the wolf’s footprints. Trends Endocrinol Metab. 2018, Mar;29(3):137-139, [Impact factor (IF) 10,893 ; NIH Relative Citation Ratio (RCR)-]
  3. Marroqui L, Dos Santos RS, Op de Beeck A, Coomans de Brachène A, Marselli L, Marchetti P, Eizirik DL. Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes, Diabetologia 2017, Apr;60(4):656-667 [IF 6,08; RCR -]
  4. Op de beeck, A. & Eizirik, D. Viral infections in type 1 diabetes mellitus – why the β cells ? Nat Rev Endoc 2016, 12, 263-273, [IF 18,318; RCR 3,9]
  5. Marroqui L, Lopes M, dos Santos R., Grieco F, Roivainen M, Richardson S, Morgan N, Eizirik DL. and Op de beeck A, Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells. eLife 2015, 4: e06990 [IF 8,303; RCR 0,88]
  6. Marroqui L, Dos Santos R, Fløyel T, Grieco F, Santin I, Op de beeck A, Marselli L, Marchetti P, Pociot F, Eizirik D. TYK2, a candidate gene for type 1 diabetes, modulates apoptosis and the innate immune response in human pancreatic β-cells. Diabetes 2015, Nov ;64(11) :3808-17 [IF 8,784; RCR 2,08]
  7. Colli, M. L., Nogueira, T. C., Allagnat, F., Andrade Da Cunha, D., Gurzov, E. N., Cardozo, A. K., Roivainen, M., Op De Beeck, A., & Eizirik, D. L. Exposure to the Viral By- Product dsRNA or Coxsackievirus B5 Triggers Pancreatic Beta Cell Apoptosis via a Bim / Mcl-1 Imbalance. P L o S Pathogens 2011, 7(9), 1002267 [IF 9,127; RCR 1,3]
  8. Ciczora Y, Callens N, Montpellier C, Bartosch B, Cosset FL, , Dubuisson J, Op de Beeck A. Contribution of the charged residues of hepatitis C virus glycoprotein E2 transmembrane domain to the functions of the E1E2 heterodimer. J Gen Virol. 2005 Oct;86(Pt 10):2793-8 [IF 3,013; RCR 0,85]
  9. Op De Beeck, A., Rouillé, Y., Caron, M., Duvet, S., & Dubuisson, J. The transmembrane domains of the prM and E proteins of yellow fever virus are endoplasmic reticulum localization signals. Journal of virology 2004, 78(22), 12591-12602 [IF 5,398; RCR 0,42]
  10. Op De Beeck, A., Voisset, C., Bartosch, B., Ciczora, Y., Cocquerel, L., Keck, Z.- Y., Foung, S. K. H., Cosset, F.-L., & Dubuisson, J. Characterization of functional hepatitis C virus envelope glycoproteins. Journal of virology 2004., 78(6), 2994-3002 [IF 5,398; RCR 4,11]