title: Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells.
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.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Hong Kong Jockey Club Clinical Research Centre, Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.
authors.forename: Helen K W
authors.initials: HK
authors.lastname: Law
authors.forename: Chung Yan
authors.initials: CY
authors.lastname: Cheung
authors.forename: Hoi Yee
authors.initials: HY
authors.lastname: Ng
authors.forename: Sin Fun
authors.initials: SF
authors.lastname: Sia
authors.forename: Yuk On
authors.initials: YO
authors.lastname: Chan
authors.forename: Winsie
authors.initials: W
authors.lastname: Luk
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.forename: J S Malik
authors.initials: JS
authors.lastname: Peiris
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002469:Cell Separation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D003713:Dendritic Cells / Q000166:cytology*; D004789:Enzyme Activation; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007249:Inflammation; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000166:cytology*; D016133:Polymerase Chain Reaction; D021122:Protein Subunits / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D016898:Interferon-alpha; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D021122:Protein Subunits; D012367:RNA, Viral; D018664:Interleukin-12; D012313:RNA; D016899:Interferon-beta; D007371:Interferon-gamma; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases