Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

How to cite: 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. Preprints 2023, 2023030241. https://doi.org/10.20944/preprints202303.0241.v1. 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. Preprints 2023, 2023030241. https://doi.org/10.20944/preprints202303.0241.v1.

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

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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