Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques

PLoS Pathogens

Michael G Katze¹  Thomas Teal¹  Brandon Rain¹  Tracey Baas¹  Albert D Osterhaus²  Bart L Haagmans²  Anna de Lang²  Lonneke M Leijten² 

[1] Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, United States of America;Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands

关键词: Macaque;    SARS coronavirus;    Gene expression;    Phosphorylation;    SARS;    Immune response;    Cytokines;    Chemokines;   

DOI  :  10.1371/journal.ppat.0030112

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.

【 授权许可】

CC BY