PubMed Journals: BMC Infect Dis
Source: PMID: 15357874
⇦ ⇨ BMC Infect Dis. 2004 Sep 9;4:34.
A human in vitro model system for investigating
genome-wide host responses to SARS
Ng LF(1), Hibberd ML, Ooi EE, Tang KF, Neo
SY, Tan J, Murthy KR, Vega VB, Chia JM,
Liu ET, Ren EC.
(1) Genome Institute of Singapore, 60 Biopolis
Street, Genome, #02-01, Singapore 138672.
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.
DOI: 10.1186/1471-2334-4-34 PMCID: PMC518965
PMID: 15357874 [Indexed for MEDLINE]