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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2366-2374.
Prepublished online as a Blood First Edition Paper on April 28, 2005; DOI 10.1182/blood-2004-10-4166.


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IMMUNOBIOLOGY

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

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

From the Department of Paediatrics and Adolescent Medicine, the Department of Microbiology, and the Department of Pathology, Hong Kong Jockey Club Clinical Research Centre, Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China.

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 1{alpha} [MIP-1{alpha}], 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.


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