Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells

Ka Wai Helen Law, Yan Cheung Chung, Yee Ng Hoi, Fun Sia Sin, On Chan Yuk, Winsie Luk, John M. Nicholls, J. S.Malik Peiris, Yu Lung Lau

Research output: Journal article publicationJournal articleAcademic researchpeer-review

280 Citations (Scopus)

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 α [IFN-α], IFN-β, IFN-γ, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor α [TNF-α] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1α [MIP-1α], 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 upregulation could represent a mechanism of immune evasion by SARS-CoV.
Original languageEnglish
Pages (from-to)2366-2374
Number of pages9
JournalBlood
Volume106
Issue number7
DOIs
Publication statusPublished - 1 Oct 2005

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this