Abstract
Lymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was observed. Using cytopathic assays, no increase in virus titer was detected in infected DCs and cell-culture supernatant, confirming that virus replication was incomplete. No induction of apoptosis or maturation was detected in SARS-CoV-infected DCs. The SARS-CoV-infected DCs showed low expression of antiviral cytokines (interferon alpha [IFN-alpha], IFN-beta, IFN-gamma, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor alpha [TNF-alpha] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1alpha [MIP-1alpha], regulated on activation normal T cell expressed and secreted [RANTES]), interferon-inducible protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The lack of antiviral cytokine response against a background of intense chemokine up-regulation could represent a mechanism of immune evasion by SARS-CoV.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis
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Caspase 3
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Caspases / biosynthesis
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Cell Separation
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Cells, Cultured
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Chemokine CCL2 / biosynthesis
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5 / biosynthesis
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Chemokines / biosynthesis*
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Cytokines / metabolism
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DNA Primers / chemistry
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Dendritic Cells / cytology*
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Enzyme Activation
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Flow Cytometry
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Fluorescent Antibody Technique, Indirect
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Humans
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Inflammation
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Interferon-alpha / biosynthesis
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Interferon-beta / biosynthesis
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Interferon-gamma / biosynthesis
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Interleukin-12 / biosynthesis
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Interleukin-12 / metabolism
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Interleukin-12 Subunit p40
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Interleukin-6 / biosynthesis
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Leukocytes, Mononuclear / cytology
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Macrophage Inflammatory Proteins / biosynthesis
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Microscopy, Electron, Transmission
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Microscopy, Fluorescence
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Monocytes / cytology*
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Polymerase Chain Reaction
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Protein Subunits / biosynthesis
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RNA / metabolism
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RNA, Viral / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Severe acute respiratory syndrome-related coronavirus / genetics
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Severe acute respiratory syndrome-related coronavirus / metabolism*
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Time Factors
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Up-Regulation*
Substances
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Chemokine CCL2
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5
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Chemokines
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Cytokines
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DNA Primers
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Interferon-alpha
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Interleukin-12 Subunit p40
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Interleukin-6
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Macrophage Inflammatory Proteins
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Protein Subunits
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RNA, Viral
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Interleukin-12
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RNA
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Interferon-beta
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Interferon-gamma
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CASP3 protein, human
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Caspase 3
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Caspases