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Unit 17: Influenza and Other Respiratory Viruses

Head:
Thorsten Wolff
Deputy:
Ralf Dürrwald

The unit is responsible for the surveillance of and research into influenza viruses and other major respiratory viral pathogens in Germany. The virological surveillance of circulating influenza viruses is carried out by the National Reference Centre for Influenza, which is part of the unit, within the framework of the National German Influenza Working Group. Every year up to 5,000 samples from patients with influenza-like illness are investigated here, which are sent by the sentinel network of general practitioners and paediatricians. The samples are also being investigated on a routine basis also for the presence of respiratory syncytial virus, human metapneumovirus, adenovirus and rhino/entoroviruses. Diagnostic typing/subtypings, sequencing and antigenic characterisation of circulating viruses enable a rapid detection of antigenic drift variants and mutant viruses resistant against licensed antiviral agents. Furthermore, the unit conducts complementary molecular virological studies to investigate the viral gene functions that control the virulence, tropism and host specificity of human and animal pathogenic influenza viruses. A specific focus is on the contribution of host factors of virus propagation and viral mechanisms that sabotage innate immune defences. The activities of the unit are integrated into the European Influenza Surveillance Network (EISN) and support the annual vaccine recommendations by WHO. At the same time they contribute to a better understanding of viral pathogens and the derivation of new strategies for the prophylaxis and therapy of respiratory virus diseases.

Tasks, Projects

Surveillance and molecular epidemiology

Molecular pathogenesis

  • Characterisation of gene functions of the influenza virus to suppress defence reactions of innate immunity
  • Analyses of host specificity and tropism of human and animal pathogenic influenza viruses
  • Studies on cellular signalling pathways in cells infected with influenza viruses
  • Identification and investigation of host factors of influenza viruses
  • Development of new approaches to the therapy and prophylaxis of virus influenza

Participation in various research and educational networks

Date: 24.01.2019

Publications

  • Spannenkrebs M, Dürrwald R, Klessinger S, Ramani-Schulzki S, Kohlsdorf K, Schick J, Mildenberger I, Biere B, Duwe S, Wedde M, Pfaff G (2018): Todesfall eines Kindes im Rahmen eines Influenza-Ausbruchs in einem Kindergarten
    Epid. Bull. 2018 (22): 205–208. doi: 10.17886/EpiBull-2018-028. more

  • Kissling E, Valenciano M, Pozo F, Vilcu AM, Reuß A, Rizzo C, Larrauri A, Horváth JK, Brytting M, Domegan L, Korczyńska M, Meijer A, Machado A, Ivanciuc A, Višekruna Vučina V, van der Werf S, Schweiger B et al.; I-MOVE/I-MOVE+ study team (2018): 2015/16 I-MOVE/I-MOVE+ multicentre case control study in Europe: moderate vaccine effectiveness estimates against influenza A(H1N1)pdm09 and low estimates against lineage mismatched influenza B among children
    Influenza Other Respir. Viruses 12 (4): 423-437. Epub 2017 Nov 10. doi: 10.1111/irv.12520. more

  • Obodai E, Odoom JK, Adiku T, Goka B, Wolff T, Biere B, Schweiger B, Reiche J (2018): The significance of human respiratory syncytial virus (HRSV) in children from Ghana with acute lower respiratory tract infection: A molecular epidemiological analysis, 2006 and 2013–2014
    PLoS One 13 (9): e0203788. Epub Sep 10. doi: 10.1371/journal.pone.0203788. more

  • Núñez RD, Budt M, Saenger S, Paki K, Arnold U, Sadewasser A, Wolff T (2018): The RNA helicase DDX6 associates with RIG-I to augment induction of antiviral signaling
    Int. J. Mol. Sci. 19 (7): pii: E1877. Epub Jun 26. doi: 10.3390/ijms19071877. more

  • Rath B, Chen X, Spies V, Muehlhans S, Obermeier P, Tief F, Seeber L, Karsch K, Milde J, Skopnik H, Schweiger B, Duwe S (2017): Prospective surveillance of antiviral resistance in hospitalized infants less than 12 months of age with A(H3N2) influenza infection and treated with oseltamivir
    Antivir. Ther. 22: 515-522. Epub Feb 16. doi: 10.3851/IMP3141. more

  • Bhatia S, Lauster D, Bardua M, Ludwig K, Angioletti-Uberti S, Popp N, Hoffmann U, Paulus F, Budt M, Stadtmüller M, Wolff T et al. (2017): Linear polysialoside outperforms dendritic analogs for inhibition of influenza virus infection in vitro and in vivo
    Biomaterials 138: 22–34. Epub May 20. doi: 10.1016/j.biomaterials.2017.05.028. more

  • Sadewasser A, Paki K, Eichelbaum K, Bogdanow B, Saenger S, Budt M, Lesch M, Hinz KP, Herrmann A, Meyer TF, Karlas A, Selbach M, Wolff T (2017): Quantitative proteomic approach identifies Vpr binding protein as novel host factor supporting influenza A virus infections in human cells
    Mol. Cell. Proteomics 16 (5): 728–742. EpubMar 13. doi: 10.1074/mcp.M116.065904. more

  • Schierhorn KL, Jolmes F, Bespalowa J, Saenger S, Peteranderl C, Dzieciolowski J, Budt M, Pleschka S, Herrmann A, Herold S, Wolff T (2017): Influenza A virus virulence depends on two amino acids in the N-terminal domain of its NS1 protein facilitating inhibition of PKR
    J. Virol. 91 (10): e00198-17. Epub Mar 1. doi: 10.1128/JVI.00198-17. more

  • Broberg E, Hungnes O, Schweiger B et al. (2016): Improving influenza virological surveillance in Europe: strain-based reporting of antigenic and genetic characterisation data, 11 European countries, influenza season 2013/14
    Euro Surveill. 21 (41): pii=30370. Epub Oct 13. doi: 10.2807/1560-7917.ES.2016.21.41.30370. more

  • Peteranderl C, Morales-Nebreda L, Selvakumar B, Lecuona E, Vadász I, Morty RE, Schmoldt C, Bespalowa J, Wolff T et al. (2016): Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection
    J. Clin. Invest. 126 (4): 1566–1580. Epub Mar 21. doi: 10.1172/JCI83931. more

  • Wedde M, Biere B, Wolff T, Schweiger B (2015): Evolution of the hemagglutinin expressed by human influenza A(H1N1)pdm09 and A(H3N2) viruses circulating between 2008-2009 and 2013-2014 in Germany
    Int. J. Med. Microbiol. 305 (7): 762-775. Epub Aug 21. doi: 10.1016/j.ijmm.2015.08.030. more

  • Reiche J, Böttcher S, Diedrich S, Buchholz U, Buda S, Haas W, Schweiger B, Wolff T (2015): Low-level circulation of enterovirus D68-associated acute respiratory infections, Germany, 2014
    Emerg. Infect. Dis. 21 (05): 837–841. doi: 10.3201/eid2105.141900. more

  • Boergeling Y, Rozhdestvensky TS, Schmolke M, Resa-Infante P, Robeck T, Randau G, Wolff T et al. (2015): Evidence for a novel mechanism of influenza virus-induced type I interferon expression by a defective RNA-encoded protein
    PLoS Pathog. 11 (5): e1004924. Epub May 29. doi: 10.1371/journal.ppat.1004924. more

  • Hocke AC, Becher A, Knepper J, Peter A, Holland G, Tönnies M, Bauer TT, Schneider P, Neudecker J, Muth D, Wendtner CM, Rückert JC, Drosten C, Gruber AD, Laue M, Suttorp N, Hippenstiel S, Wolff T (2013): Emerging human Middle East Respiratory Syndrome coronavirus causes widespread infection and alveolar damage in human lungs
    Am. J. Respir. Crit. Care Med. 188 (7): 882–886. Epub Oct 1. doi: 10.1164/rccm.201305-0954LE. more

  • Weinheimer VK, Becher A, Tönnies M, Holland G, Knepper J, Bauer TT, Schneider P, Neudecker J, Rückert JC, Szymanski K, Temmesfeld-Wollbrueck B, Gruber AD, Bannert N, Suttorp N, Hippenstiel S, Wolff T, Hocke AC (2012): Influenza A viruses target type II pneumocytes in the human lung
    J. Infect. Dis. 206 (11): 1685-1694. Epub Jul 24. doi: 10.1093/infdis/jis455. more

  • Corman VM, Müller MA, Costabel U, Timm J, Binger T, Meyer B, Kreher P, Lattwein E, Eschbach-Bludau M, Nitsche A, Bleicker T, Landt O, Schweiger B, Drexler JF, Osterhaus AD, Haagmans BL, Dittmer U, Bonin F, Wolff T, Drosten C (2012): Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections
    Euro Surveill. 17 (49): pii: 20334. more

  • Rath B, von Kleist M, Tief F, Karsch K, Tuerk E, Muehlhans S, Louis F, Skopnik H, Schweiger B, Duwe S (2012): Virus load kinetics and resistance development during oseltamivir treatment in infants and children infected with influenza A (H1N1) 2009 and influenza B viruses
    Pediatr. Infect. Dis. J. 31 (9): 899-905. Epub May 10. doi: 10.1097/INF.0b013e31825c7304. more

  • Duwe S, Wedde M, Birkner P, Schweiger B (2011): Genotypic and phenotypic resistance of pandemic A/H1N1 influenza viruses circulating in Germany
    Antiviral Res. 89 (1): 115–118. Epub 2010 Nov 9. doi:10.1016/j.antiviral.2010.11.001. more

  • Abt M, de Jonge J, Laue M, Wolff T (2011): Improvement of H5N1 influenza vaccine viruses: Influence of internal gene segments of avian and human origin on production and hemagglutinin content
    Vaccine 29 (32): 5153-5162. Epub May 30. doi:10.1016/j.vaccine.2011.05.036. more

  • Karlas A, Machuy N, Shin Y, Pleissner KP, Artarini A, Heuer D, Becker D, Khalil H, Ogilvie LA, Hess S, Mäurer AP, Müller E, Wolff T, Rudel T, Meyer TF (2010): Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication
    Nature 463 (7282): 818-822. Epub Jan 17. more

  • Zielecki F, Semmler I, Kalthoff D, Voss D, Mauel S, Gruber AD, Beer M, Wolff T (2010): Virulence determinants of avian H5N1 influenza A virus in mammalian and avian hosts: The role of the C-terminal ESEV motif in the viral NS1 protein
    J. Virol. 84 (20): 10708-10718. Epub Aug 4. more

  • Schulze M, Nitsche A, Schweiger B, Biere B (2010): Diagnostic approach for the differentiation of the pandemic influenza A(H1N1)v virus from recent human influenza viruses by real-time PCR
    PLoS One 5 (4): e9966. more