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Virus-host interactions

Virus-caused diseases are a major threat to human health. We focus on proteins coded by human immunodeficiency virus (HIV), Dengue virus (DENV), hepatitis C virus (HCV) and SARS-Coronavirus (SARS-CoV) the causative agents of acquired immunodeficiency syndrome (AIDS), of dengue fever, of chronic hepatitis, and of the severe acute respiratory syndrome (SARS), respectively. Despite a highly evolved immune defense, once infected, humans are e.g. not able to clear HIV-1 from the body, and also most of the HCV exposed persons develop a chronic infection. Still, there is an urgent need for preventive vaccines as well as safe and effective antivirals against these viruses.

Viruses selectively modulate functions of their respective host cells to ensure viral replication and persistence. Viral proteins interfere with various cellular signaling pathways or cellular processes like apoptosis and autophagy, thereby often combating the antiviral defense mechanisms of the infected host cell. We investigate the role of virus-coded regulatory or nonstructural proteins that target or abuse cellular proteins or even cellular membranes in the interest of virus replication or for their defense against the host immune system.

Our research is focused on distinct viral proteins and their respective cellular interaction partners. In the long run, a better understanding of these interactions down to the atomic level will lead to new concepts for innovative antiviral therapies.

We are using a broad spectrum of methods including tools from molecular biology, cellular biology and biophysics. The institute is well equipped for recombinant protein expression/purification, phage display or yeast two-hybrid screens. Structural and dynamic aspects are elucidated by liquid state NMR spectroscopy or in close cooperation with our in-house solid state NMR spectroscopy and X-ray crystal structure facilities. Together with our external cooperation partners, located, e.g., at the Universities of Düsseldorf, Germany, and Tel Aviv, Israel, we are scrutinizing the biological relevance of the studied interactions between virus proteins and host factors.

Further information:

undefinedTeam Hänel

undefinedArbeitsgruppe Hoffmann

undefinedArbeitsguppe König

undefinedArbeitsgruppe Schwarten


  • Coronado MA, Eberle RJ, Bleffert N, Feuerstein S, Olivier DS, de Moraes FR, Willbold D, Arni RK 
    Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition. 
    Antiviral Res. 160, 118-125 (2018) 
  • Hung Y-F, Schwarten M, Hoffmann S, Willbold D, Sklan EH, Koenig BW 
    Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes 
    Viruses 7, 4119-4130 (2015) 
  • Chien T-H, Chiang Y-L, Chen C-P, Henklein P, Hänel K, Hwang I-S, Willbold D, Fischer WB 
    Assembling an ion channel: ORF 3a from SARS-CoV 
    Biopolymers 99, 628-635 (2013) 
  • Do H, Wittlich M, Glück JM, Möckel L, Willbold D, Koenig BW, Heise H 
    Full-length Vpu and human CD4(372-433) in phospholipid bilayers as seen by magic angle spinning NMR. 
    Biol. Chem. 394, 1453-1463 (2013) 
  • Schwarten M, Solyom Z, Feuerstein S, Aladag A, Hoffmann S, Willbold D, Brutscher B 
    Interaction of non-structural protein 5A of hepatitis C virus with SH3 domains using non-canonical binding sites 
    Biochemistry 52, 6160-6168 (2013) 
  • Stern O, Hung Y-F, Valdau O, Yaffe Y, Harris E, Hoffmann S, Willbold D, Sklan E 
    An N-terminal amphipathic helix in the Dengue virus nonstructural protein 4A mediates oligomerization and is essential for replication. 
    J. Virol. 87, 4080-4085 (2013) 
  • Feuerstein S, Solyom Z, Aladag A, Favier A, Schwarten M, Hoffmann S, Willbold D, Brutscher B 
    Transient structure and SH3 interaction sites in an intrinsically disordered fragment of the hepatitis C virus protein NS5A. 
    J. Mol. Biol. 420, 310-323 (2012) 
  • Kammula E, Moetter J, Gorgels A, Jonas E, Hoffmann S, Willbold D 
    Brain transcriptome-wide screen for HIV-1 Nef protein interaction partners reveals various membrane-associated proteins. 
    PLoS ONE 7, e51578 (2012) 
    full text open access  
  • Singh S, Möckel L, Thiagarajan-Rosenkranz P, Wittlich M, Willbold D, Koenig B 
    Mapping the interaction between the cytoplasmic domains of HIV-1 VpU and human CD4 using NMR spectroscopy. 
    FEBS J. 279, 3705-3714 (2012) 
  • Feuerstein S, Solyom Z, Aladag A, Hoffmann S, Willbold D, Brutscher B 
    1H, 13C, and 15N resonance assignment of a 179 residue fragment of hepatitis C virus nonstructural protein 5A 
    Biomol. NMR Assign. 53, 241-243 (2011) 
  • Pfannkuche A, Büther K, Karthe J, Poenisch M, Bartenschlager R, Trilling M, Hengel H, Willbold D, Häussinger D, Bode JG 
    c-Src is required for complex formation between the hepatitis C virus encoded proteins NS5A and NS5B – a prerequisite for replication. 
    Hepatology 53, 1127-1136 (2011) 
  • Glück JM, Hoffmann S, Koenig BW, Willbold D 
    Single Vector System for Efficient N-myristoylation of Recombinant Proteins in E. coli 
    PLoS ONE 5, e10081 (2010) 
    full text open access  
    The plasmids in this publication can be received via https://www.addgene.org/Dieter_Willbold/ 
  • Wittlich M, Thiagarajan P, Koenig BW, Hartmann R, Willbold D 
    NMR structure of the transmembrane and cytoplasmic domains of human CD4 in micelles. 
    Biochim Biophys Acta 1798, 122-127 (2010) 
  • Wittlich M, Koenig BW, Stoldt M, Schmidt H, Willbold D 
    NMR structural characterization of HIV-1 virus protein U cytoplasmic domain in the presence of dodecylphosphatidylcholine micelles. 
    FEBS J. 276, 6560-75 (2009) 
  • Wittlich M, Koenig BW, Willbold D 
    Structural consequences of phosphorylation of two serine residues in the cytoplasmic domain of HIV-1 VpU. 
    J. Pept. Sci. 14, 804-10 (2008) 
  • Hänel K, Willbold D 
    SARS-CoV accessory protein 7a directly interacts with human LFA-1. 
    Biol. Chem. 388, 1325-1332 (2007) 
  • Hoffmann S, Jonas E, Konig S, Preusser-Kunze A, Willbold D 
    Nef protein of human immunodeficiency virus type 1 binds its own myristoylated N-terminus. 
    Biol. Chem. 366, 181-183 (2007) 
  • Stangler T, Tran T, Hoffmann S, Schmidt H, Jonas E, Willbold D 
    Competitive displacement of full-length HIV-1 Nef from Hck SH3 domain by a high affinity artificial peptide. 
    Biol. Chem. 388, 611-615 (2007) 
  • Wittlich M, Koenig BW, Hoffmann S, Willbold D 
    Structural characterisation of the transmembrane and cytoplasmic domains of human CD4. 
    Biochim Biophys Acta 1768, 2949-60 (2007) 
  • Wittlich M, Wiesehan K, Koenig BW, Willbold D 
    Expression, purification, and membrane reconstitution of a CD4 fragment comprising the transmembrane and cytoplasmic domains of the receptor. 
    Protein Expr. Purif. 55, 198-207 (2007) 
  • Hänel K, Stangler T, Stoldt M, Willbold D 
    Solution structure of the X4 protein coded by the SARS related coronavirus reveals an immunoglobulin like fold and suggests a binding activity to integrin I domains. 
    J. Biomed. Sci. 13, 281-293 (2006) 
  • Lemaitre V, Wray V, Willbold D, Watts A, Fischer WB 
    Full length Vpu from HIV-1: Combining molecular dynamics simulations with NMR spectroscopy. 
    J. Biomol. Struct. Dyn. 23, 485-496 (2006) 
  • Briese L, Preusser A, Willbold D 
    Mapping the binding site of full length HIV-1 Nef on human Lck SH3 by NMR spectroscopy. 
    J. Biomed. Sci. 12, 451-456 (2005) 
  • Harrer E, Bäuerle M, Ferstl B, Chaplin P, Petzold B, Mateo L, Handley A, Tzatzaris M, Vollmar J, Bergmann S, Rittmaier M, Eismann K, Müller S, Kalden JR, Spriewald B, Willbold D, Harrer T 
    Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment interruption. 
    Antiviral Therapy 10, 285-300 (2005) 
  • Willbold D 
    Interaction of HIV-1 Nef with human CD4 and Lck. 
    in 'Viral membrane proteins: structure, function and drug design', W. Fischer, ed. Kluwer Academic Publishers, New York , (2005) 
  • Engler A, Stangler T, Willbold D 
    Structure of human immunodeficiency virus type 1 Vpr (34-51) peptide in micelle containing aqueous solution. 
    Eur. J. Biochem. 269, 3264-3269 (2002) 
  • Preusser A, Briese L, Willbold D 
    Presence of a helix in human CD4 cytoplasmic domain promotes binding to HIV-1 Nef protein. Biochem. 
    Biochem. Biophys. Res. Comm. 292, 734-740 (2002) 
  • Engler A, Stangler T, Willbold D 
    Solution structure of human immunodeficiency virus type 1 Vpr (13-33) peptide in micelles. 
    Eur. J. Biochem. 268, 389-395 (2001) 
  • Jonas G, Hoffmann S, Willbold D 
    Binding of phage displayed HIV-1 Tat to TAR RNA in the presence of Cyclin T1. 
    J. Biomed. Sci. 8, 340-346 (2001) 
  • Preusser A, Briese L, Baur AS, Willbold D 
    Direct in vitro binding of full-length HIV-1 Nef protein to CD4 cytoplasmic domain. 
    J. Virol. 75, 3960-3964 (2001) 
  • Hoffmann S, Willbold D 
    A selection system to study protein-RNA interactions: Functional display of HIV-1 Tat protein on filamentous bacteriophage M13 
    Biochem. Biophys. Res. Comm. 235, 806-811 (1997) 
  • Metzger AU, Bayer B, Willbold D, Hoffmann S, Frank RW, Goody RS, Rösch P 
    The interaction of HIV-1 Tat (32-72) with its target RNA: A Fluorescence and Nuclear Magnetic Resonance Study 
    Biochem. Biophys. Res. Comm. 241, 31-36 (1997) 
  • Willbold D, Hoffmann S, Rösch P 
    Secondary structure and tertiary fold of the human immunodeficiency virus protein U (Vpu) cytoplasmic domain in solution 
    Eur. J. Biochem. 245, 581-588 (1997) 
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