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Stefan Kunz lab

Stefan Kunz, PhD, Associate Professor
++41 (0)21 314 7743
stefan.kunz@chuv.ch

Research topics

Human pathogenic arenaviruses

The arenaviruses are an important family of viruses that merit significant attention as important human pathogens. The prototypic arenavirus lymphocytic choriomeningitis virus is a prevalent human pathogen of particular concern in pediatric and transplantation medicine. Over the past decades several arenaviruses have emerged as causative agents of severe viral hemorrhagic fevers that belong to the most devastating human diseases and cause considerable suffering in many countries of the Developing World. The Old World arena virus Lassa virus is the most prevalent human pathogen among the arenaviruses with several hundred thousand infections per year in Africa with thousands of deaths. The South American hemorrhagic fever viruses Junin, Machupo, Guanarito, and Sabia have emerged as etiological agents of severe hemorrhagic fevers in Latin America. There is no licensed vaccine available and therapeutic options are restricted, resulting in 15-30% mortality in hospitalized patients. New pathogenic arenaviruses emerge with on average one new species being discovered every three years, representing a serious concern for public health.

Our research combines the study of fundamental mechanisms of virus-host cell interaction of human pathogenic arenaviruses (Basic Research) with the development of novel anti-viral strategies against these important pathogens (Applied Research).

 

Current lab members
Name Position Contact
Stefan Kunz, Ph.D Associate Professor stefan.kunz@chuv.ch
Sylvia Rothenberger, Ph.D Project scientist sylvia.rothenberger-aubert@chuv.ch
Antonella Pasquato, Ph.D Senior Research Associate antonella.pasquato@chuv.ch
Marie-Laurence Moraz Ph.D student marie-laurence.moraz@chuv.ch
Ana Rita Gonçalves Ph.D student ana-rita.goncalves@chuv.ch
Dominique Burri Ph.D student dominique.burri@chuv.ch
Christelle Pythoud Ph.D student christelle.pythoud@chuv.ch
Joel Ramos da Palma Ph.D student Joel.Palma@chuv.ch

 

Selected Publications


2013

1: Burri DJ, Pasquato A, da Palma JR, Igonet S, Oldstone MB, Kunz S.
    The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain.
Virology. 2013 Feb 5;436(1):127-33. doi: 10.1016/j.virol.2012.10.038.
2: Burri DJ, Ramos da Palma J, Seidah NG, Zanotti G, Cendron L, Pasquato A, Kunz S.
    Differential recognition of Old World and New World arenavirus envelope glycoproteins by subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P).
Journal of virology 87: 6406-6414.
3: Goncalves AR, Moraz ML, Pasquato A, Helenius A, Lozach PY, Kunz S.
    Role of DC-SIGN in Lassa Virus Entry into Human Dendritic Cells
Journal of virology 87:11504-11515.
4: Pasquato A, da Palma JR, Galan C, Seidah NG, Kunz S.
    Viral envelope glycoprotein processing by proprotein convertases.
Antiviral research. 99:49-60

2012

1: Burri DJ, Pasqual G, Rochat C, Seidah NG, Pasquato A, Kunz S.
    Molecular characterization of the processing of arenavirus envelope glycoprotein precursors by subtilisin kexin isozyme-1/site-1 protease.
J Virol. 2012 May;86(9):4935-46.
2: Burri DJ, da Palma JR, Kunz S, Pasquato A.
    Envelope glycoprotein of arenaviruses.
Viruses. 2012 Oct 17;4(10):2162-81. doi: 10.3390/v4102162.
3: Moraz ML, Pythoud C, Turk R, Rothenberger S, Pasquato A, Campbell KP, Kunz S.
    Cell entry of Lassa virus induces tyrosine phosphorylation of dystroglycan.
Cell Microbiol. 2012 Nov 29. doi: 10.1111/cmi.12078.
4: Pasquato A, Burri DJ, Kunz S.
    Current drug discovery strategies against arenavirus infections.
Expert Rev Anti Infect Ther. 2012 Nov;10(11):1297-309. doi: 10.1586/eri.12.117.
5: Pasquato A, Rochat C, Burri DJ, Pasqual G, de la Torre JC, Kunz S.
    Evaluation of the anti-arenaviral activity of the subtilisin kexin isozyme-1/site-1 protease inhibitor PF-429242.
Virology. 2012 Feb 5;423(1):14-22.
6: Pythoud C, Rodrigo WW, Pasqual G, Rothenberger S, Martínez-Sobrido L, de la Torre JC, Kunz S.
    Arenavirus nucleoprotein targets interferon regulatory factor-activating kinase IKK{varepsilon}
J Virol. 2012 Apr 24. [Epub ahead of print]
7: Rojek JM, Moraz ML, Pythoud C, Rothenberger S, Van der Goot FG, Campbell KP, Kunz S.
    Binding of Lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan.
Cell Microbiol. 2012 Mar 9. doi: 10.1111/j.1462-5822.2012.01784.x.

2011

1: Dylla, D. E., Xie, L., Michele, D. E., Kunz, S., and McCray, P. B., Jr.
    Altering alpha-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism.
Genet Vaccines Ther 9, 8.
2: Hara, Y., Balci-Hayta, B., Yoshida-Moriguchi, T., Kanagawa, M., Beltran-Valero de Bernabe, D., Gundesli, H., Willer, T., Satz, J. S., Crawford, R. W., Burden, S. J., Kunz, S., Oldstone, M. B., Accardi, A., Talim, B., Muntoni, F., Topaloglu, H., Dincer, P., and Campbell, K. P.
    A dystroglycan mutation associated with limb-girdle muscular dystrophy.
N Engl J Med 364(10), 939-46.
3: Hara, Y., Kanagawa, M., Kunz, S., Yoshida-Moriguchi, T., Satz, J. S., Kobayashi, Y. M., Zhu, Z., Burden, S. J., Oldstone, M. B., and Campbell, K. P.
    Like-acetylglucosaminyltransferase (LARGE)-dependent modification of dystroglycan at Thr-317/319 is required for laminin binding and arenavirus infection.
Proc Natl Acad Sci U S A 108(42), 17426-31.
4: Lee, A.M., Pasquato, A., Kunz, S.
    Novel approaches in anti-arenaviral drug development.
Virology 411(2), 163-9.
5: Moraz, M. L., and Kunz, S.
    Pathogenesis of arenavirus hemorrhagic fevers.
Expert Rev Anti Infect Ther 9(1), 49-59.
6: Pasqual, G., Burri, D.J., Pasquato, A., de la Torre, J.C., Kunz, S.
    The role of the host cell's unfolded protein response in arenavirus infection.
J Virol 85(4), 1662-70.
7: Pasqual, G., Rojek, J. M., Masin, M., Chatton, J. Y., and Kunz, S.
    Old world arenaviruses enter the host cell via the multivesicular body and depend on the endosomal sorting complex required for transport.
PLoS Pathog 7(9), e1002232.
8: Pasquato, A., Burri, D. J., Traba, E. G., Hanna-El-Daher, L., Seidah, N. G., and Kunz, S.
    Arenavirus envelope glycoproteins mimic autoprocessing sites of the cellular proprotein convertase subtilisin kexin isozyme-1/site-1 protease.
Virology 417(1), 18-26.
9: Urata, S., Yun, N., Pasquato, A., Paessler, S., Kunz, S., and de la Torre, J. C.
    Antiviral activity of a small-molecule inhibitor of arenavirus glycoprotein processing by the cellular site 1 protease.
J Virol 85(2), 795-803.

2010

1: Liou, L-Y., Walsh, K.B., Vartanian, A.R., Beltran-Valero de Bernabe, D., Welch, M., Campbell, K.P., Oldstone, M.B., and Kunz, S.
    Functional Glycosylation of Dystroglycan is Crucial for Thymocyte Development in the Mouse.
PlosONE: Mar 29; 5(3):e9915.
2: Rojek, J. M., Pasqual, G., Sanchez, A. B., Nguyen, N. T., de la Torre, J. C., and Kunz, S.
    Targeting the proteolytic processing of the viral glycoprotein precursor is a promising novel antiviral strategy against arenaviruses.
J. Virol. 84(1):573-84.
3: Urata, S., Yun, N., Pasquato, A., Paessler, S., Kunz, S., de la Torre, J.C.
    Antiviral activity of a small-molecule inhibitor of arenavirus glycoprotein processing by the cellular site 1 protease.
J. Virol. 85:795-803.
4: Yoshida-Moriguchi, T., Yu, L., Stalnaker, S. H., Davis, S., Kunz, S., Madson, M., Oldstone, M. B., Schachter, H., Wells, L., and Campbell, K. P.
    O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding.
Science 327(5961):88-92.

2009

1: Han, R., Kanagawa, M., Yoshida-Moriguchi, T., Rader, E. P., Ng, R. A., Michele, D. E., Muirhead, D. E., Kunz, S., Moore, S. A., Iannaccone, S. T., Miyake, K., McNeil, P. L., Mayer, U., Oldstone, M. B., Faulkner, J. A., and Campbell, K. P.
    Basal lamina strengthens cell membrane integrity via the laminin G domain-binding motif of alpha-dystroglycan.
Proc. Natl Acad. Sci. USA 106(31):12573-9.
2: Kunz, S.
    Receptor binding and cell entry of Old World arenaviruses reveal novel aspects of virus-host interaction.
Virology 387(2):245-9.
3: Kunz, S.
    The role of the vascular endothelium in arenavirus haemorrhagic fevers. Thromb Haemost
Thromb. Haemost. 102(6):1024-9.
4: Whitby, L. R., Lee, A. M., Kunz, S., Oldstone, M. B., and Boger, D. L.
    Characterization of lassa virus cell entry inhibitors: determination of the active enantiomer by asymmetric synthesis.
Bioorg. Med. Chem. Lett. 19(14):3771-4.

2008

1: Kunz, S. and de la Torre, J.C.
    Arenavirus infection in the nervous system: uncovering principles of virus-host interaction and viral pathogenesis.
In: Neutropic Viral Infections, C.C. Reiss (Ed.). Cambridge University Press
2: Lee, A.M. Rojek, J.M., Gundersen, A., Juteau, M., Vaillant, A. and Kunz, S.
    Inhibition of cellular entry and spread of lymphocytic choriomeningitis virus by phosphorothioate oligonucleotides.
Virology. 2008 Mar 1;372(1):107-17.
3: Lee, A.M., Rojek, J.M., Spiropoulou, C.F., Gundersen, A.T., Jin, W., Shaginian, A., York, J., Nunberg, J.H., Boger, D.L., Oldstone, M.B., Kunz S.
    Unique small molecule entry inhibitors of hemorrhagic fever arena viruses.
J. Biol. Chem. 2008 Jul 4;283(27):18734-42.
4: Rojek, J.M. and Kunz, S.
    Cellular entry by human pathogenic arenaviruses.
Cell Microbiol. 2008 Apr;10(4):828-35.
5: Rojek, J.M., Lee, A.M., Nguyen, N., Spiropoulou, C.F., Kunz S.
    Site 1 protease is required for proteolytic processing of the glycoproteins of the South American hemorrhagic fever viruses Junin, Machupo, and Guanarito.
J. Virol. 2008 Jun;82(12):6045-51.
6: Rojek, J.M., Perez, M., and Kunz, S.
    Cellular entry of lymphocytic choriomeningitis virus.
J. Virol. 2008 Feb;82(3):1505-17.
7: Rojek, J.M., Sanchez, A.B., Thao, N.N., de la Torre, J.C., Kunz S.
    Different mechanisms of cell entry by human pathogenic Old World and New World arenaviruses.
J. Virol. 2008 Aug;82(15):7677-87.
8: Trifilo MJ, Sanchez-Alavez M, Solforosi L, Bernard-Trifilo J, Kunz S, McGavern D, Oldstone MB.
    Scrapie-induced defects in learning and memory of transgenic mice expressing anchorless prion protein are associated with alterations in the gamma aminobutyric acid-ergic pathway.
J. Virol. 2008 Oct;82(20):9890-9.

2007

1: Butticaz, C., Michielin, O., Wyniger, J., Telenti, A., and S. Rothenberger
    Silencing of both beta-TRCP1 and HOS (beta-TRCP2) is required to suppress HIV-1 VPU-mediated CD4 down-modulation.
J. Virol. 2007 81:1502-5.
2: Capul, A.A. Perez, M. Kunz S., Buchmeier, M.J. Burke E. and de la Torre, J.C
    Arenavirus Z-GP association requires Z myristoylation but not functional RING or L domains.
J. Virol. 81:9451-9460.
3: Georgel, P., Jiang, Z., Kunz, S., Janssen, E., Mols, J., Hoebe, K, Bahram,. S., Oldstone, M.B., Beutler, B.
    Vesicular stomatitis virus glycoprotein G activates a specific antiviral Toll-like receptor 4-dependent pathway.
Virology. 2007 Jun 5;362(2):304-13.
4: Rojek, J.M. Campbell, K.P. Oldstone, M.B.A., and Kunz S.
    Old World Arenavirus infection interferes with the expression of functional a-dystroglycan in the host cell.
Mol. Biol. Cell. 18:4493-4507.
5: Rojek, J.M., Spiropoulou, C.F., Campbell, K.P., and Kunz, S.
    Old World arenaviruses mimic the molecular mechanism of receptor recognition used by a-dystroglycans’s host-derived ligands
J. Virol. 81:5685-5695.

2006

1: Kunz, S., Rojek, J.M. Roberts, A.J. McGavern, D.B. Oldstone, M.B.A., and de la Torre, J.C
    Altered central nervous system gene expression caused by congenitally acquired persistent infection with lymphocytic choriomeningitis virus.
J. Virol. 80:9082-9092.
2: Rojek, J.M., Spiropoulou, C.F., and Kunz, S.
    Characterization of the cellular receptors for the South American hemorrhagic fever viruses Junin, Guanarito, and Machupo.
Virology 349:476-491.

2005

1: Kunz, S. and de la Torre, J.C.
    Novel antiviral strategies to combat human arenavirus infections.
Current Molecular Medicine 5:735-751.
2: Kunz, S., Rojek, J. M., Kanagawa, M., Spiropoulou, C. F., Campbell, K. P., and Oldstone, M. B. A.
    Post-translational modification of a-dystroglycan, the cellular receptor for arenaviruses by the glycosyltransferase LARGE is critical for virus binding.
J. Virol. 79:14282-14296.
3: Kunz, S., Rojek, J. M., Perez, M., Spiropoulou, C.F., and Oldstone, M. B. A.
    Characterization of the interaction of Lassa fever virus with its cellular receptor a-dystroglycan.
J. Virol. 79:5979-5987.


Last Update on 04.11.2013 - Publication credits - Legal information