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Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques

Nature Medicine volume 10, pages 290–293 (2004)Cite this article

Abstract

The 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-α (IFN-α) 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-α yielded intermediate results. We therefore suggest that pegylated IFN-α protects type 1 pneumocytes from SCV infection, and should be considered a candidate drug for SARS therapy

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Figure 1: Histological lesions and immunohistochemical and ultrastructural detection of SCV in lungs of experimentally infected macaques.
Figure 2: Antiviral activity of pegylated IFN-α against SCV in vitro and its biological activity in macaques.
Figure 3: Effect of pegylated IFN-α on SCV excretion in macaques.
Figure 4: Effect of pegylated IFN-α on SCV replication, viral antigen expression and histological lesions in lungs of SCV-infected macaques at 4 d.p.i.

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Acknowledgements

We thank S. Bruijns, J.M. Vrolijk, G. Aron, F. van der Panne, R. Dias d'Ullois and D. Fekkes for assistance, and J.D. Laman for advice on immunohistochemistry.

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Author notes

  1. Bart L Haagmans and Thijs Kuiken: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Virology, Erasmus Medical Centre, PO Box 1738, Rotterdam, 3000 DR, The Netherlands

    Bart L Haagmans, Thijs Kuiken, Byron E Martina, Ron A M Fouchier, Guus F Rimmelzwaan, Geert van Amerongen & Albert D M E Osterhaus

  2. Department of Immunology, Erasmus Medical Centre, PO Box 1738, Rotterdam, 3000 DR, The Netherlands

    Debby van Riel

  3. Department of Pathology, Erasmus Medical Centre, PO Box 1738, Rotterdam, 3000 DR, The Netherlands

    Ton de Jong

  4. Department of Viral Diseases & Vaccine Control, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan

    Shigeyuki Itamura & Masato Tashiro

  5. Department of Microbiology and Pathology, Queen Mary Hospital, University of Hong Kong SAR, China

    Kwok-Hung Chan

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  1. Bart L Haagmans
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  2. Thijs Kuiken
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Correspondence to Albert D M E Osterhaus.

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Haagmans, B., Kuiken, T., Martina, B. et al. Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat Med 10, 290–293 (2004). https://doi.org/10.1038/nm1001

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