Dataset Information

Analysis of Nipah virus replication and host proteome response patterns in differentiated porcine airway epithelial cells cultured at the air-liquid interface

ABSTRACT: Respiratory tract epithelium infection is considered crucial for airborne transmission of Nipah virus (NiV). Knowledge about infection dynamics and host responses to NiV infection in respiratory tract epithelia is scarce. Various studies in non-differentiated primary respiratory tract cells or cell lines indicate limitations in interferon responses. However, comprehensive studies determining complex reaction patterns in differentiated respiratory tract epithelia to understand efficient NiV replication and spread in swine populations are lacking. Here we characterized infection and spread of NiV in differentiated primary porcine bronchial epithelial cells (PBEC) cultivated at the air-liquid-interface (ALI). After initial infection of only a few apical cells, lateral spread for 12 days with disruption of the epithelium was observed without releasing substantial amounts of infectious virus from the apical or basal sides. Deep time course proteomics revealed pronounced upregulation of genes related to type I/II interferon (IFN), immunoproteasomal subunits, TAP-mediated peptide transport and MHC I antigen presentation, whereas spliceosomal factors were downregulated. We deduce a model in which NiV replication in pig bronchial epithelia is slowed by a potent and broad type I/II interferon host response with concurrent conversion from 26S proteasomal to immunoproteasomal antigen processing and improved MHC I presentation as a crucial step in adaptive immunity priming. Moreover, strong cytopathic effects observed in infected areas could reflect focal release of cell-associated NiV. Cell-associated NiV may translate into the source of efficient airborne viral spread in vivo with a high local infectious dose leading to high and fast spread of NiV throughout pig herds.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Respiratory Epithelial Cell

DISEASE(S): Nipah Virus Encephalitis

SUBMITTER: Axel Karger

LAB HEAD: Axel Karger

PROVIDER: PXD032673 | Pride | 2023-05-10

REPOSITORIES: Pride

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Publications

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

Müller Martin M Fischer Kerstin K Woehnke Elisabeth E Zaeck Luca M LM Prönnecke Christoph C Knittler Michael R MR Karger Axel A Diederich Sandra S Finke Stefan S

Viruses 20230413 4

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 respiratory tract epithelia is scarce. Studies in non-differentiated primary respiratory tract cells or cell lines indicate insufficient interferon (IFN) responses. However, studies are lacking in the determination of complex host response patterns in differentiated respiratory tract epithelia for the understandi ...[more]

PMID: 37112941

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Project description:Occasional transmission of highly pathogenic avian H5N1 influenza viruses to humans causes severe pneumonia with high mortality. To better understand the mechanisms via which H5N1 viruses induce severe disease in humans, we infected cynomolgus macaques with six different H5N1 strains isolated from human patients and compared their pathogenicity and the global host responses to the virus infection. Although all H5N1 viruses replicated in the respiratory tract, there was substantial heterogeneity in their replicative ability and in the disease severity induced, which ranged from asymptomatic to fatal. A comparison of global gene expression between severe and mild disease cases indicated that interferon-induced up-regulation of genes related to innate immunity, apoptosis, and antigen processing/presentation in the early phase of infection was limited in severe disease cases, although interferon expression was up-regulated in both severe and mild cases. Furthermore, co-expression analysis of microarray data, which reveals the dynamics of host responses during the infection, demonstrated that the limited expression of these genes early in infection led to a failure to suppress virus replication and to the hyperinduction of genes related to immunity, inflammation, coagulation, and homeostasis in the late phase of infection, resulting in a more severe disease. Our data suggest that the attenuated interferon-induced activation of innate immunity, apoptosis, and antigen presentation in the early phase of H5N1 virus infection leads to subsequent severe disease outcome. Bronchial brushes for microarray studies were obtained from female cynomolgus macaques infected with influenza viruses. Three animals per group were inoculated with one of three H5N1 influenza viruses (VN3028II, VN30259 or VN3040). The early phase of infection refers to timepoints Pre (prior to infection), 1, and 3 days post-infection. The late phase of infection refers to days 5 and 7 post-infection. Samples collected prior to infection (labeled as Pre) served as control data for each infection group.

Dataset Information

Analysis of Nipah virus replication and host proteome response patterns in differentiated porcine airway epithelial cells cultured at the air-liquid interface

Publications

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

Similar Datasets

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