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2005 ; 79
(12
): 7819-26
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Cytokine responses in severe acute respiratory syndrome coronavirus-infected
macrophages in vitro: possible relevance to pathogenesis
#MMPMID15919935
Cheung CY
; Poon LL
; Ng IH
; Luk W
; Sia SF
; Wu MH
; Chan KH
; Yuen KY
; Gordon S
; Guan Y
; Peiris JS
J Virol
2005[Jun]; 79
(12
): 7819-26
PMID15919935
show ga
The pathogenesis of severe acute respiratory syndrome (SARS) remains unclear.
Macrophages are key sentinel cells in the respiratory system, and it is therefore
relevant to compare the responses of human macrophages to infections with the
SARS coronavirus (SARS-CoV) and other respiratory viruses. Primary human
monocyte-derived macrophages were infected with SARS-CoV in vitro. Virus
replication was monitored by measuring the levels of positive- and
negative-strand RNA, by immunofluorescence detection of the SARS-CoV
nucleoprotein, and by titration of the infectious virus. The gene expression
profiles of macrophages infected with SARS-CoV, human coronavirus 229E, and
influenza A (H1N1) virus were compared by using microarrays and real-time
quantitative reverse transcriptase PCR. Secreted cytokines were measured with an
enzyme-linked immunosorbent assay. SARS-CoV initiated viral gene transcription
and protein synthesis in macrophages, but replication was abortive and no
infectious virus was produced. In contrast to the case with human coronavirus
229E and influenza A virus, there was little or no induction of beta interferon
(IFN-beta) in SARS-CoV-infected macrophages. Furthermore, SARS-CoV induced the
expression of chemokines such as CXCL10/IFN-gamma-inducible protein 10 and
CCL2/monocyte chemotactic protein 1. The poor induction of IFN-beta, a key
component of innate immunity, and the ability of the virus to induce chemokines
could explain aspects of the pathogenesis of SARS.