Lassa virus: host cell tropism and molecular pathogenesis

Research area: Molecular Virology

Lassa virus (LASV) is a zoonotic, hemorrhagic fever-causing virus that is endemic to West Africa.  Approved vaccines or specific antiviral drugs suitable to combat these infections are not available. The primary transmission route of LASV from its reservoir host to humans involves direct exposure to virus-containing rodent excretions. Although the initial infection involves the respiratory tract through inhalation of contaminated dust or fomites, information on LASV infection of human respiratory epithelial cells is limited. In the current funding period, the Strecker group observed that LASV infects polarized bronchial epithelial cells via the apical or basolateral side, while progeny virus particles are released predominantly from the apical surface. Goblet cells and basal cells were identified as initial LASV target cells in a primary human bronchial epithelial cell culture model. Together with collaborators, the Strecker group also solved the three-dimensional architecture of LASV virions and the spike envelope glycoprotein using high-resolution electron cryomicroscopy and tomography techniques.

Project-related publications of the investigator:

  • Thom R, Tipton T, Strecker T, Hall Y, Akoi Bore J, Maes P, Raymond Koundouno F, Fehling SK, Krahling V, Steeds K, Varghese A, Bailey G, Matheson M, Kouyate S, Cone M, Moussa Keita B, Kouyate S, Richard Ablam A, Laenen L, Vergote V, Guiver M, Timothy J, Atkinson B, Ottowell L, Richards KS, Bosworth A, Longet S, Mellors J, Pannetier D, Duraffour S, Munoz-Fontela C, Sow O, Koivogui L, Newman E, Becker S, Sprecher A, Raoul H, Hiscox J, Henao-Restrepo AM, Sakoba K, Magassouba N, Gunther S, Kader Konde M, Carroll MW. 2021. Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study. Lancet Infect Dis 21:507-516.
  • Olayemi A, Adesina AS, Strecker T, Magassouba N, Fichet-Calvet E. 2020. Determining Ancestry between Rodent- and Human-Derived Virus Sequences in Endemic Foci: Towards a More Integral Molecular Epidemiology of Lassa Fever within West Africa. Biology (Basel) 9.
  • Muller H, Fehling SK, Dorna J, Urbanowicz RA, Oestereich L, Krebs Y, Kolesnikova L, Schauflinger M, Krahling V, Magassouba N, Fichet-Calvet E, Ball JK, Kaufmann A, Bauer S, Becker S, von Messling V, Strecker T. 2020. Adjuvant formulated virus-like particles expressing native-like forms of the Lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity. NPJ Vaccines 5:71.
  • Blok AJ, Gurnani P, Xenopoulos A, Burroughs L, Duncan J, Urbanowicz RA, Tsoleridis T, Muller-Krauter H, Strecker T, Ball JK, Alexander C, Alexander MR. 2020. Polymer microarrays rapidly identify competitive adsorbents of virus-like particles. Biointerphases 15:061005.
  • Timothy JWS, Hall Y, Akoi-Bore J, Diallo B, Tipton TRW, Bower H, Strecker T, Glynn JR, Carroll MW. 2019. Early transmission and case fatality of Ebola virus at the index site of the 2013-16 west African Ebola outbreak: a cross-sectional seroprevalence survey. Lancet Infect Dis 19:429-438.
  • Whitmer SLM, Strecker T, Cadar D, Dienes HP, Faber K, Patel K, Brown SM, Davis WG, Klena JD, Rollin PE, Schmidt-Chanasit J, Fichet-Calvet E, Noack B, Emmerich P, Rieger T, Wolff S, Fehling SK, Eickmann M, Mengel JP, Schultze T, Hain T, Ampofo W, Bonney K, Aryeequaye JND, Ribner B, Varkey JB, Mehta AK, Lyon GM, 3rd, Kann G, De Leuw P, Schuettfort G, Stephan C, Wieland U, Fries JWU, Kochanek M, Kraft CS, Wolf T, Nichol ST, Becker S, Stroher U, Gunther S. 2018. New Lineage of Lassa Virus, Togo, 2016. Emerg Infect Dis 24:599-602.
  • Watanabe Y, Raghwani J, Allen JD, Seabright GE, Li S, Moser F, Huiskonen JT, Strecker T, Bowden TA, Crispin M. 2018. Structure of the Lassa virus glycan shield provides a model for immunological resistance. Proc Natl Acad Sci U S A 115:7320-7325.
  • Sauerhering L, Muller H, Behner L, Elvert M, Fehling SK, Strecker T, Maisner A. 2017. Variability of interferon-lambda induction and antiviral activity in Nipah virus infected differentiated human bronchial epithelial cells of two human donors. J Gen Virol 98:2447-2453.
  • Huber M, Suprunenko T, Ashhurst T, Marbach F, Raifer H, Wolff S, Strecker T, Viengkhou B, Jung SR, Obermann HL, Bauer S, Xu HC, Lang PA, Tom A, Lang KS, King NJC, Campbell IL, Hofer MJ. 2017. IRF9 Prevents CD8(+) T Cell Exhaustion in an Extrinsic Manner during Acute Lymphocytic Choriomeningitis Virus Infection. J Virol 91.