Nature Medicine
10, 290 - 293 (2004)
Published online: 22 February 2004; | doi:10.1038/nm1001
Pegylated interferon- protects type 1 pneumocytes against SARS coronavirus infection in macaquesBart L Haagmans1, 6, Thijs Kuiken1, 6, Byron E Martina1, Ron A M Fouchier1, Guus F Rimmelzwaan1, Geert van Amerongen1, Debby van Riel2, Ton de Jong3, Shigeyuki Itamura4, Kwok-Hung Chan5, Masato Tashiro4
& Albert D M E Osterhaus11
Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam, Netherlands. 2
Department of Immunology, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam, Netherlands. 3
Department of Pathology, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam, Netherlands. 4
Department of Viral Diseases & Vaccine Control, National Institute of Infectious Diseases, Tokyo 208-0011, Japan. 5
Department of Microbiology and Pathology, Queen Mary Hospital, University of Hong Kong SAR, China. 6
These authors contributed equally to this work.
Correspondence should be addressed to Albert D M E Osterhaus a.osterhaus@erasmusmc.nlThe primary cause of severe acute respiratory syndrome (SARS) is a newly discovered coronavirus1,
2,
3,
4,
5,
6,
7. Replication of this SARS coronavirus (SCV) occurs mainly in the lower respiratory tract, and causes diffuse alveolar damage2,
7,
8. Lack of understanding of the pathogenesis of SARS has prevented the rational development of a therapy against this disease. Here we show extensive SCV antigen expression in type 1 pneumocytes of experimentally infected cynomolgus macaques (Macaca fascicularis) at 4 d postinfection (d.p.i.), indicating that this cell type is the primary target for SCV infection early in the disease, and explaining the subsequent pulmonary damage. We also show that prophylactic treatment of SCV-infected macaques with the antiviral agent pegylated interferon- (IFN-) significantly reduces viral replication and excretion, viral antigen expression by type 1 pneumocytes and pulmonary damage, compared with untreated macaques. Postexposure treatment with pegylated IFN- yielded intermediate results. We therefore suggest that pegylated IFN- protects type 1 pneumocytes from SCV infection, and should be considered a candidate drug for SARS therapy
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