PubMed Journals: BMC Infect Dis

  Source:		PMID: 15357874
  Download:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC518965/pdf/1471-2334-4-34.pdf

    		BMC Infect Dis. 2004 Sep 9;4:34.
			A human in vitro model system for investigating
			genome-wide host responses to SARS
			coronavirus infection.

			Ng LF(1), Hibberd ML, Ooi EE, Tang KF, Neo
			SY, Tan J, Murthy KR, Vega VB, Chia JM,
			Liu ET, Ren EC.

			Author Information
			(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]

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