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Journal of Virology, June 2005, p. 7819-7826, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7819-7826.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cytokine Responses in Severe Acute Respiratory Syndrome Coronavirus-Infected Macrophages In Vitro: Possible Relevance to Pathogenesis

Chung Y. Cheung,1 Leo L. M. Poon,1 Iris H. Y. Ng,1 Winsie Luk,1 Sin-Fun Sia,1 Mavis H. S. Wu,1 Kwok-Hung Chan,1 Kwok-Yung Yuen,1 Siamon Gordon,2 Yi Guan,1 and Joseph S. M. Peiris1*

Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China,1 Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom2

Received 19 August 2004/ Accepted 9 February 2005

The pathogenesis of severe acute respiratory syndrome (SARS) remains unclear. Macrophages are key sentinel cells in the respiratory system, and it is therefore relevant to compare the responses of human macrophages to infections with the SARS coronavirus (SARS-CoV) and other respiratory viruses. Primary human monocyte-derived macrophages were infected with SARS-CoV in vitro. Virus replication was monitored by measuring the levels of positive- and negative-strand RNA, by immunofluorescence detection of the SARS-CoV nucleoprotein, and by titration of the infectious virus. The gene expression profiles of macrophages infected with SARS-CoV, human coronavirus 229E, and influenza A (H1N1) virus were compared by using microarrays and real-time quantitative reverse transcriptase PCR. Secreted cytokines were measured with an enzyme-linked immunosorbent assay. SARS-CoV initiated viral gene transcription and protein synthesis in macrophages, but replication was abortive and no infectious virus was produced. In contrast to the case with human coronavirus 229E and influenza A virus, there was little or no induction of beta interferon (IFN-ß) in SARS-CoV-infected macrophages. Furthermore, SARS-CoV induced the expression of chemokines such as CXCL10/IFN-{gamma}-inducible protein 10 and CCL2/monocyte chemotactic protein 1. The poor induction of IFN-ß, a key component of innate immunity, and the ability of the virus to induce chemokines could explain aspects of the pathogenesis of SARS.

* Corresponding author. Mailing address: Department of Microbiology, University Pathology Building, Queen Mary Hospital, Pokfulam Road, Hong Kong, Special Administrative Region, People's Republic of China. Phone: (852) 28554888. Fax: (852) 28551241. E-mail: malik{at}hkucc.hku.hk.

Journal of Virology, June 2005, p. 7819-7826, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7819-7826.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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