Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques.
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.
Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam, Netherlands.
Bart L
BL
Haagmans
Thijs
T
Kuiken
Byron E
BE
Martina
Ron A M
RA
Fouchier
Guus F
GF
Rimmelzwaan
Geert
G
van Amerongen
Debby
D
van Riel
Ton
T
de Jong
Shigeyuki
S
Itamura
Kwok-Hung
KH
Chan
Masato
M
Tashiro
Albert D M E
AD
Osterhaus
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D000998:Antiviral Agents / Q000627:therapeutic use*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008252:Macaca fascicularis; D011092:Polyethylene Glycols; D011650:Pulmonary Alveoli / Q000166:cytology / Q000473:pathology / Q000821:virology*; D011994:Recombinant Proteins; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a