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

The primary cause of severe acute respiratory syndrome (SARS) is a newly discovered coronavirus(1,2,3,4,5,6,7). Replication of this SARS coronavirus (SCV) occurs mainly in the lower respiratory tract, and causes diffuse alveolar damage(2,7,8). Lack of understanding of the pathogenesis of SARS has pr...

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Autores principales: Haagmans, Bart L, Kuiken, Thijs, Martina, Byron E, Fouchier, Ron A M, Rimmelzwaan, Guus F, van Amerongen, Geert, van Riel, Debby, de Jong, Ton, Itamura, Shigeyuki, Chan, Kwok-Hung, Tashiro, Masato, Osterhaus, Albert D M E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095986/
https://www.ncbi.nlm.nih.gov/pubmed/14981511
http://dx.doi.org/10.1038/nm1001
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author Haagmans, Bart L
Kuiken, Thijs
Martina, Byron E
Fouchier, Ron A M
Rimmelzwaan, Guus F
van Amerongen, Geert
van Riel, Debby
de Jong, Ton
Itamura, Shigeyuki
Chan, Kwok-Hung
Tashiro, Masato
Osterhaus, Albert D M E
author_facet Haagmans, Bart L
Kuiken, Thijs
Martina, Byron E
Fouchier, Ron A M
Rimmelzwaan, Guus F
van Amerongen, Geert
van Riel, Debby
de Jong, Ton
Itamura, Shigeyuki
Chan, Kwok-Hung
Tashiro, Masato
Osterhaus, Albert D M E
author_sort Haagmans, Bart L
collection PubMed
description The primary cause of severe acute respiratory syndrome (SARS) is a newly discovered coronavirus(1,2,3,4,5,6,7). Replication of this SARS coronavirus (SCV) occurs mainly in the lower respiratory tract, and causes diffuse alveolar damage(2,7,8). 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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spelling pubmed-70959862020-03-26 Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques Haagmans, Bart L Kuiken, Thijs Martina, Byron E Fouchier, Ron A M Rimmelzwaan, Guus F van Amerongen, Geert van Riel, Debby de Jong, Ton Itamura, Shigeyuki Chan, Kwok-Hung Tashiro, Masato Osterhaus, Albert D M E Nat Med Article The primary cause of severe acute respiratory syndrome (SARS) is a newly discovered coronavirus(1,2,3,4,5,6,7). Replication of this SARS coronavirus (SCV) occurs mainly in the lower respiratory tract, and causes diffuse alveolar damage(2,7,8). 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 Nature Publishing Group US 2004-02-22 2004 /pmc/articles/PMC7095986/ /pubmed/14981511 http://dx.doi.org/10.1038/nm1001 Text en © Nature Publishing Group 2004 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Haagmans, Bart L
Kuiken, Thijs
Martina, Byron E
Fouchier, Ron A M
Rimmelzwaan, Guus F
van Amerongen, Geert
van Riel, Debby
de Jong, Ton
Itamura, Shigeyuki
Chan, Kwok-Hung
Tashiro, Masato
Osterhaus, Albert D M E
Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques
title Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques
title_full Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques
title_fullStr Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques
title_full_unstemmed Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques
title_short Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques
title_sort pegylated interferon-α protects type 1 pneumocytes against sars coronavirus infection in macaques
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095986/
https://www.ncbi.nlm.nih.gov/pubmed/14981511
http://dx.doi.org/10.1038/nm1001
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