PubMed Journals: PLoS Pathog
Source: PMID: 17696609
⇦ ⇨ PLoS Pathog. 2007 Aug 10;3(8):e112.
Functional genomics highlights differential
induction of antiviral pathways in the lungs
of SARS-CoV-infected macaques.
de Lang A(1), Baas T, Teal T, Leijten LM,
Rain B, Osterhaus AD, Haagmans BL, Katze
(1) Department of Virology, Erasmus Medical Center,
Rotterdam, The Netherlands.
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
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.
PMCID: PMC1941749 PMID: 17696609 [Indexed