Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections

Abstract

The pathogenesis of severe acute respiratory syndrome (SARS) is poorly understood and cytokine dysregulation has been suggested as one relevant mechanism to be explored. We compared the cytokine profile in Caco2 cells after infection of SARS coronavirus (SARS-CoV) with other respiratory viruses including respiratory syncytial virus (RSV), influenza A virus (FluAV), and human parainfluenza virus type 2 (hPIV2). Interferon (IFN) system (production and response) was not suppressed by SARS-CoV infection. Therefore, SARS-CoV replication was suppressed by pretreatment with IFN. SARS-CoV and RSV induced high levels of IL-6 and RANTES compared with FluAV and hPIV2. Induction level of suppressor of cytokine signaling-3 (SOCS3) by SARS-CoV was significantly lower than that by RSV in spite of the significant production of IL-6. Toll-like receptors 4 and 9, which correlate with the induction of inflammatory response, were upregulated by SARS-CoV infection. Collectively, overinduction of inflammatory cytokine and dysregulation of cytokine signaling may contribute to the immunopathology associated with "severe" inflammation in SARS.

Identification of an infectious bronchitis coronavirus strain exhibiting a classical genotype but altered antigenicity, pathogenicity, and innate immunity profile

“…In previous studies, SARS-CoV and MHV infections have been shown to trigger IFIH1 expression for MDA5 signaling4445. It has also been reported that TLR4 expression can be induced by SARS-CoV infection46. The robust expression of PRR molecules triggered by IBV 2575 AT sheds light on the molecular mechanism behind the strain’s attenuated virulence and pathogenicity.…”

Helicobacter pylori VacA Suppresses Lactobacillus acidophilus-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway

“…We identified that Socs3, a negative regulator of cytokine signaling, was among the most strongly expressed genes in macrophages stimulated with H. pylori (see Table S2 in the supplemental material). Socs3 is upregulated by several viruses, e.g., herpes simplex virus 1 (HSV-1) (38), hepatitis virus C (HCV) (39), influenza A virus (40), human immunodeficiency virus type 1 (HIV-1) (41), severe acute respiratory syndrome (SARS) virus (42), and respiratory syncytial virus (RSV) (43, 44), resulting in the inhibition of the type I interferon signaling pathway. Hence, the expression of Socs3 in macrophages stimulated with H. pylori might be an additional mechanism utilized by this pathogen to suppress cytokine signaling and thereby the activation of adaptive immunity.…”

Severe Acute Respiratory Syndrome Coronavirus Elicits a Weak Interferon Response Compared to Traditional Interferon-Inducing Viruses

“…Moreover, it has also been reported by Okabayashi et al [26] that the IFN system was not suppressed by SARS-CoV infection. The reasons for these discrepancies are still unclear.…”