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A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection.
BMC Infect Dis. 2004 Sep 09; 4:34.BI

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.

Authors+Show Affiliations

Genome Institute of Singapore, 60 Biopolis Street, Genome, #02-01, Singapore 138672. ngfp@gis.a-star.edu.sgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15357874

Citation

Ng, Lisa F P., et al. "A Human in Vitro Model System for Investigating Genome-wide Host Responses to SARS Coronavirus Infection." BMC Infectious Diseases, vol. 4, 2004, p. 34.
Ng LF, Hibberd ML, Ooi EE, et al. A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection. BMC Infect Dis. 2004;4:34.
Ng, L. F., Hibberd, M. L., Ooi, E. E., Tang, K. F., Neo, S. Y., Tan, J., Murthy, K. R., Vega, V. B., Chia, J. M., Liu, E. T., & Ren, E. C. (2004). A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection. BMC Infectious Diseases, 4, 34.
Ng LF, et al. A Human in Vitro Model System for Investigating Genome-wide Host Responses to SARS Coronavirus Infection. BMC Infect Dis. 2004 Sep 9;4:34. PubMed PMID: 15357874.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection. AU - Ng,Lisa F P, AU - Hibberd,Martin L, AU - Ooi,Eng-Eong, AU - Tang,Kin-Fai, AU - Neo,Soek-Ying, AU - Tan,Jenny, AU - Murthy,Karuturi R Krishna, AU - Vega,Vinsensius B, AU - Chia,Jer-Ming, AU - Liu,Edison T, AU - Ren,Ee-Chee, Y1 - 2004/09/09/ PY - 2004/06/11/received PY - 2004/09/09/accepted PY - 2004/9/11/pubmed PY - 2005/5/3/medline PY - 2004/9/11/entrez SP - 34 EP - 34 JF - BMC infectious diseases JO - BMC Infect. Dis. VL - 4 N2 - 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. SN - 1471-2334 UR - https://www.unboundmedicine.com/medline/citation/15357874/A_human_in_vitro_model_system_for_investigating_genome_wide_host_responses_to_SARS_coronavirus_infection_ L2 - https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-4-34 DB - PRIME DP - Unbound Medicine ER -