Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4
Haverkamp, Ann-Kathrin (University of Veterinary Medicine Hannover Foundation. Department of Pathology)
Lehmbecker, Annika (Center for Systems Neuroscience)
Spitzbarth, Ingo (Center for Systems Neuroscience)
Widagdo, Widagdo (Erasmus Medical Center. Department of Viroscience)
Haagmans, Bart L. (Erasmus Medical Center. Department of Viroscience)
Segalés Coma, Joaquim (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Vergara-Alert, Júlia (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Bensaid, Albert (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
van den Brand, Judith M. A. (Utrecht University. Department of Pathobiology)
Osterhaus, Albert D. M. E. (University of Veterinary Medicine Hannover Foundation. Research Center for Emerging Infections and Zoonoses)
Baumgärtner, Wolfgang (Center for Systems Neuroscience)

Fecha:	2018
Resumen:	Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at day four post infection. Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14 expressing cells did not co-localize with virus. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary monocytes, but overall the expression level was lower in dromedaries. The present study underlines significant species-specific manifestations of MERS and highlights ciliary loss as an important finding in dromedaries. The obtained results promote a better understanding of coronavirus infections, which pose major health challenges.
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Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Scientific reports, Vol. 8 (june 2018) , ISSN 2045-2322

DOI: 10.1038/s41598-018-28109-2
PMID: 29950581

15 p, 3.4 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Centre de Recerca en Sanitat Animal (CReSA-IRTA)
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