Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques.
Identifieur interne : 005215 ( Main/Exploration ); précédent : 005214; suivant : 005216Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques.
Auteurs : Bart L. Haagmans [Pays-Bas] ; Thijs Kuiken ; Byron E. Martina ; Ron A M. Fouchier ; Guus F. Rimmelzwaan ; Geert Van Amerongen ; Debby Van Riel ; Ton De Jong ; Shigeyuki Itamura ; Kwok-Hung Chan ; Masato Tashiro ; Albert D M E. OsterhausSource :
- Nature medicine [ 1078-8956 ] ; 2004.
Descripteurs français
- KwdFr :
- Alvéoles pulmonaires (anatomopathologie), Alvéoles pulmonaires (cytologie), Alvéoles pulmonaires (virologie), Animaux, Antigènes viraux (analyse), Antiviraux (usage thérapeutique), Humains, Interféron alpha (usage thérapeutique), Macaca fascicularis, Polyéthylène glycols, Protéines recombinantes, Réplication virale (), Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (), Virus du SRAS (immunologie), Virus du SRAS (physiologie).
- MESH :
- analyse : Antigènes viraux.
- anatomopathologie : Alvéoles pulmonaires.
- cytologie : Alvéoles pulmonaires.
- immunologie : Virus du SRAS.
- physiologie : Virus du SRAS.
- usage thérapeutique : Antiviraux, Interféron alpha.
- virologie : Alvéoles pulmonaires, Syndrome respiratoire aigu sévère.
- Animaux, Humains, Macaca fascicularis, Polyéthylène glycols, Protéines recombinantes, Réplication virale, Syndrome respiratoire aigu sévère, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antigens, Viral (analysis), Antiviral Agents (therapeutic use), Humans, Interferon alpha-2, Interferon-alpha (therapeutic use), Macaca fascicularis, Polyethylene Glycols, Pulmonary Alveoli (cytology), Pulmonary Alveoli (pathology), Pulmonary Alveoli (virology), Recombinant Proteins, SARS Virus (drug effects), SARS Virus (immunology), SARS Virus (physiology), Severe Acute Respiratory Syndrome (prevention & control), Severe Acute Respiratory Syndrome (virology), Virus Replication (drug effects).
- MESH :
- chemical , analysis : Antigens, Viral.
- chemical , therapeutic use : Antiviral Agents, Interferon-alpha.
- cytology : Pulmonary Alveoli.
- drug effects : SARS Virus, Virus Replication.
- immunology : SARS Virus.
- pathology : Pulmonary Alveoli.
- physiology : SARS Virus.
- prevention & control : Severe Acute Respiratory Syndrome.
- virology : Pulmonary Alveoli, Severe Acute Respiratory Syndrome.
- Animals, Humans, Interferon alpha-2, Macaca fascicularis, Polyethylene Glycols, Recombinant Proteins.
Abstract
The primary cause of severe acute respiratory syndrome (SARS) is a newly discovered coronavirus. Replication of this SARS coronavirus (SCV) occurs mainly in the lower respiratory tract, and causes diffuse alveolar damage. 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-alpha (IFN-alpha) 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-alpha yielded intermediate results. We therefore suggest that pegylated IFN-alpha protects type 1 pneumocytes from SCV infection, and should be considered a candidate drug for SARS therapy.
DOI: 10.1038/nm1001
PubMed: 14981511
Affiliations:
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Haagmans</name><affiliation wicri:level="3"><nlm:affiliation>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam, Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name></author><author><name sortKey="Martina, Byron E" sort="Martina, Byron E" uniqKey="Martina B" first="Byron E" last="Martina">Byron E. Martina</name></author><author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A M" last="Fouchier">Ron A M. 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Haagmans</name><affiliation wicri:level="3"><nlm:affiliation>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam, Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name></author><author><name sortKey="Martina, Byron E" sort="Martina, Byron E" uniqKey="Martina B" first="Byron E" last="Martina">Byron E. Martina</name></author><author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A M" last="Fouchier">Ron A M. Fouchier</name></author><author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F" last="Rimmelzwaan">Guus F. 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Replication of this SARS coronavirus (SCV) occurs mainly in the lower respiratory tract, and causes diffuse alveolar damage. 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-alpha (IFN-alpha) 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-alpha yielded intermediate results. We therefore suggest that pegylated IFN-alpha protects type 1 pneumocytes from SCV infection, and should be considered a candidate drug for SARS therapy.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li></country><region><li>Hollande-Méridionale</li></region><settlement><li>Rotterdam</li></settlement></list><tree><noCountry><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name><name sortKey="De Jong, Ton" sort="De Jong, Ton" uniqKey="De Jong T" first="Ton" last="De Jong">Ton De Jong</name><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A M" last="Fouchier">Ron A M. Fouchier</name><name sortKey="Itamura, Shigeyuki" sort="Itamura, Shigeyuki" uniqKey="Itamura S" first="Shigeyuki" last="Itamura">Shigeyuki Itamura</name><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name><name sortKey="Martina, Byron E" sort="Martina, Byron E" uniqKey="Martina B" first="Byron E" last="Martina">Byron E. Martina</name><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D M E" last="Osterhaus">Albert D M E. Osterhaus</name><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F" last="Rimmelzwaan">Guus F. Rimmelzwaan</name><name sortKey="Tashiro, Masato" sort="Tashiro, Masato" uniqKey="Tashiro M" first="Masato" last="Tashiro">Masato Tashiro</name><name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name></noCountry><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L" last="Haagmans">Bart L. Haagmans</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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