Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates

Christian Selinger, Jennifer Tisoncik-Go, Vineet Menachery, Sudhakar Agnihothram, G. Lynn Law, Jean Chang, Sara M. Kelly, Pavel Sova, Ralph S. Baric, Michael G. Katze

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic and pathogenic potential of emerging coronaviruses in humans. Clinical features of Middle East respiratory syndrome (MERS) include atypical pneumonia and progressive respiratory failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV SA 1 and MERS-CoV Eng 1. Results: Using topological techniques, including persistence homology and filtered clustering, we performed a comparative transcriptional analysis of human Calu-3 cell host responses to the different MERS-CoV strains, with MERS-CoV Eng 1 inducing early kinetic changes, between 3 and 12 hours post infection, compared to MERS-CoV SA 1. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated Calu-3 transcriptomics, we identified differential innate responses, including up-regulation of extracellular remodeling genes following MERS-CoV Eng 1 infection and differential pro-inflammatory responses. Conclusions: Through our genomics-based approach, we found topological differences in the kinetics and magnitude of the host response to MERS-CoV SA 1 and MERS-CoV Eng 1, with differential expression of innate immune and pro-inflammatory responsive genes as a result of IFN, TNF and IL-1α signaling. Predicted activation for STAT3 mediating gene expression relevant for epithelial cell-to-cell adherens and junction signaling in MERS-CoV Eng 1 infection suggest that these transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity during MERS-CoV infection.

Original languageEnglish (US)
Article number1161
JournalBMC Genomics
Volume15
Issue number1
DOIs
StatePublished - Dec 22 2014
Externally publishedYes

Fingerprint

Coronavirus Infections
Systems Analysis
Cytokines
Severe Acute Respiratory Syndrome
Infection
Coronavirus
Epithelial Cells
Gene Expression
Adherens Junctions
Intercellular Junctions
Middle East
Zoonoses
Viral Proteins
Virus Diseases

Keywords

  • Computational topology
  • Coronavirus
  • Cytokine simulation
  • MERS-CoV
  • Transcriptomics

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates. / Selinger, Christian; Tisoncik-Go, Jennifer; Menachery, Vineet; Agnihothram, Sudhakar; Law, G. Lynn; Chang, Jean; Kelly, Sara M.; Sova, Pavel; Baric, Ralph S.; Katze, Michael G.

In: BMC Genomics, Vol. 15, No. 1, 1161, 22.12.2014.

Research output: Contribution to journalArticle

Selinger, C, Tisoncik-Go, J, Menachery, V, Agnihothram, S, Law, GL, Chang, J, Kelly, SM, Sova, P, Baric, RS & Katze, MG 2014, 'Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates', BMC Genomics, vol. 15, no. 1, 1161. https://doi.org/10.1186/1471-2164-15-1161
Selinger, Christian ; Tisoncik-Go, Jennifer ; Menachery, Vineet ; Agnihothram, Sudhakar ; Law, G. Lynn ; Chang, Jean ; Kelly, Sara M. ; Sova, Pavel ; Baric, Ralph S. ; Katze, Michael G. / Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates. In: BMC Genomics. 2014 ; Vol. 15, No. 1.
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AU - Law, G. Lynn

AU - Chang, Jean

AU - Kelly, Sara M.

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