Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Analysis of Nipah Virus Replication and Host Proteome Response Patterns in Differentiated Porcine Airway Epithelial Cells Cultured at the Air-Liquid Interface

Martin Müller
,
Kerstin Fischer
ORCID logo ,
Elisabeth Woehnke
,
Luca M. Zaeck
ORCID logo ,
Christoph Prönnecke
,
Michael R. Knittler
ORCID logo ,
Axel Karger
ORCID logo ,
Sandra Diederich
ORCID logo ,
Stefan Finke
* ORCID logo
Version 1 : Received: 13 March 2023 / Approved: 14 March 2023 / Online: 14 March 2023 (02:50:52 CET)

A peer-reviewed article of this Preprint also exists.

Müller, M.; Fischer, K.; Woehnke, E.; Zaeck, L.M.; Prönnecke, C.; Knittler, M.R.; Karger, A.; Diederich, S.; Finke, S. Analysis of Nipah Virus Replication and Host Proteome Response Patterns in Differentiated Porcine Airway Epithelial Cells Cultured at the Air–Liquid Interface. Viruses 2023, 15, 961. Müller, M.; Fischer, K.; Woehnke, E.; Zaeck, L.M.; Prönnecke, C.; Knittler, M.R.; Karger, A.; Diederich, S.; Finke, S. Analysis of Nipah Virus Replication and Host Proteome Response Patterns in Differentiated Porcine Airway Epithelial Cells Cultured at the Air–Liquid Interface. Viruses 2023, 15, 961.

Abstract

Respiratory tract epithelium infection plays a primary role in Nipah virus (NiV) pathogenesis and transmission. Knowledge about infection dynamics and host responses to NiV infection in respir-atory tract epithelia is scarce. Studies in non-differentiated primary respiratory tract cells or cell lines indicate insufficient interferon (IFN) responses. However, studies are lacking to determin-ing complex host response patterns in differentiated respiratory tract epithelia to understand NiV replication and spread in swine. Here we characterized infection and spread of NiV in differenti-ated primary porcine bronchial epithelial cells (PBEC) cultivated at the air-liquid-interface (ALI). After the initial infection of only a few apical cells, lateral spread for 12 days with epithelium disruption was observed without releasing substantial amounts of infectious virus from the api-cal or basal sides. Deep time course proteomics revealed pronounced upregulation of genes re-lated to type I/II- IFN, immunoproteasomal subunits, TAP-mediated peptide transport and MHC I antigen presentation. Spliceosomal factors were downregulated. We propose a model in which NiV replication in PBEC is slowed by a potent and broad type I/II-IFN host response with con-version from 26S proteasomes to immunoproteasomal antigen processing and improved MHC I presentation for adaptive immunity priming. NiV induced cytopathic effects could reflect the focal release of cell-associated NiV, which may contribute to efficient airborne viral spread between pigs.

Keywords

Nipah virus; air-liquid interface culture; respiratory epithelium; mass spectrometry; immune response

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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