article Open Access (gold) EN 2004-09-09

A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection

Abstract

BACKGROUND: The molecular basis of severe acute respiratory syndrome (SARS) coronavirus (CoV) induced pathology is still largely unclear. Many SARS patients suffer respiratory distress brought on by interstitial infiltration and frequently show peripheral blood lymphopenia and occasional leucopenia. One possible cause of this could be interstitial inflammation, following a localized host response. In this study, we therefore examine the immune response of SARS-CoV in human peripheral blood mononuclear cells (PBMCs) over the first 24 hours. METHODS: PBMCs from normal healthy donors were inoculated in vitro with SARS-CoV and the viral replication kinetics was studied by real-time quantitative assays. SARS-CoV specific gene expression changes were examined by high-density oligonucleotide array analysis. RESULTS: We observed that SARS-CoV was capable of infecting and replicating in PBMCs and the kinetics of viral replication was variable among the donors. SARS-CoV antibody binding assays indicated that SARS specific antibodies inhibited SARS-CoV viral replication. Array data showed monocyte-macrophage cell activation, coagulation pathway upregulation and cytokine production together with lung trafficking chemokines such as IL8 and IL17, possibly activated through the TLR9 signaling pathway; that mimicked clinical features of the disease. CONCLUSIONS: The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis.

Topics

COVID-19 Clinical Research Studies 0.58 SARS-CoV-2 and COVID-19 Research 0.34 Long-Term Effects of COVID-19 0.02

Field: Medicine · Subfield: Infectious Diseases

Keywords

Immunology,Peripheral blood mononuclear cell,Chemokine,Immune system,Biology,Pathogenesis,Viral replication,Coronavirus,Virology,Medical microbiology

MeSH Terms

AnimalsAnimalsAnimalsChlorocebus aethiopsChlorocebus aethiopsChlorocebus aethiopsHumansHumans

UN Sustainable Development Goals

  • Good health and well-being (0.76)

All Available Versions

  • PDF Landing page — BMC Infectious Diseases publishedVersion cc-by
  • Landing page — PubMed publishedVersion
  • Landing page — LSHTM Research Online (London School of Hygiene and Tropical Medicine) acceptedVersion
  • Landing page — Europe PMC (PubMed Central) submittedVersion
  • Landing page — PubMed Central submittedVersion
  • Landing page — National University of Singapore submittedVersion

Citations by Year

202520242023202220212020201720142012
12372023132
2.75
FWCI
89%
Normalized Pctile
44
References
11
Authors

Continue on JournalsHub

Put what you just read into practice with these free tools.

Comparison Shortlist
0 journals
Est. APC Budget: $0
Compare Now
Compare 0 Open → Clear
Save your viewing history
You've browsed several journals this session. Sign in to track them in one place and get weekly impact-factor updates.
Save with Google