Type 1 diabetes and viruses
GROUP LEADER: ANNE OP DE BEECK
Dr Op de beeck joined her virologist expertise to the team of Decio Eizirik devoted to the study of type 1 diabetes, an autoimmune disease caused by a progressive immune-mediated loss of pancreatic β-cell mass via apoptosis.
Group leader:
Anne Op de Beeck, PhD
Anne Op de beeck 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, 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 tenured position as researcher at the Centre National de la Recherche Scientifique (CNRS), France.
She is currently detached from the CNRS and holds an appointment as Professor of the Faculty of Medicine, Université Libre de Bruxelles.
Research Interests
The triggering of type 1 diabetes 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 type 1 diabetes. In line with this, many candidate genes for type 1 diabetes regulate antiviral responses in both β-cells and the immune system.
The main research focus of the Op de beeck group are the characterization of virus-induced β-cell dysfunction and death and the identification of factors involved in β-cell permissiveness to viral infection.
In collaboration with Eizirik, Op de beeck unveiled the mechanisms 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 type 1 diabetes. She also recently described that Coxsackievirus tailors the unfolded protein response to ER stress to favor viral amplification in pancreatic β-cells.
Selected Publications
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. J Innate Immun. 2019;11(4):375-390. doi: 10.1159/000496034. [IF 4,085]
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)-]
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 -]
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]
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]
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]
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]
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]
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]
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]
