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J Gen Virol. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment.
[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
J Gen Virol. 2013 Sep 28. [Epub ahead of print]
Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment.
Lau SK, Lau CC, Chan KH, Li CP, Chen H, Jin DY, Chan JF, Woo PC, Yuen KY.
Source: The University of Hong Kong.
Abstract
The high mortality associated with the novel Middle East respiratory syndrome coronavirus (MERS-CoV) has raised questions on the possible role of cytokine storm in its pathogenesis. Although recent studies showed that MERS-CoV infection is associated with attenuated interferon response, no induction of inflammatory cytokines was demonstrated during early phase of infection. To study both early and late cytokine responses associated with MERS-CoV infection, we measured the mRNA levels of eight cytokine genes (TNF-α, IL-1β, IL-6, IL-8, IFN-β, MCP-1, TGF-β and IP-10) in cell lysates of polarized airway epithelial, Calu-3, cells infected with MERS-CoV or SARS-CoV up to 30 h post infection. Among the eight cytokine genes, IL-1β, IL-6 and IL-8 induced by MERS-CoV were markedly higher than those induced by SARS-CoV at 30 h, while TNF-α, IFN-β and IP-10 induced by SARS-CoV were markedly higher than those induced by MERS-CoV at 24 and 30 h in infected Calu-3 cells. The activation of IL-8 and attenuated IFN-β response by MERS-CoV were also confirmed by protein measurements in the culture supernatant when compared to SARS-CoV and Sendai virus. To further confirm the attenuated antiviral response, cytokine response was compared to HCoV-229E in embryonal lung fibroblast, HFL, cells, which also revealed higher IFN-β and IP-10 levels induced by HCoV-229E than MERS-CoV at 24 and 30 h. While our data supported recent findings that MERS-CoV elicits attenuated innate immunity, this represents the first report to demonstrate delayed proinflammatory cytokine induction by MERS-CoV. Our results provide insights into the pathogenesis and treatment of MERS-CoV infections.
KEYWORDS: 229E, MERS, SARS, coronavirus, human
PMID: 24077366 [PubMed - as supplied by publisher]
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J Gen Virol. 2013 Sep 28. [Epub ahead of print]
Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment.
Lau SK, Lau CC, Chan KH, Li CP, Chen H, Jin DY, Chan JF, Woo PC, Yuen KY.
Source: The University of Hong Kong.
Abstract
The high mortality associated with the novel Middle East respiratory syndrome coronavirus (MERS-CoV) has raised questions on the possible role of cytokine storm in its pathogenesis. Although recent studies showed that MERS-CoV infection is associated with attenuated interferon response, no induction of inflammatory cytokines was demonstrated during early phase of infection. To study both early and late cytokine responses associated with MERS-CoV infection, we measured the mRNA levels of eight cytokine genes (TNF-α, IL-1β, IL-6, IL-8, IFN-β, MCP-1, TGF-β and IP-10) in cell lysates of polarized airway epithelial, Calu-3, cells infected with MERS-CoV or SARS-CoV up to 30 h post infection. Among the eight cytokine genes, IL-1β, IL-6 and IL-8 induced by MERS-CoV were markedly higher than those induced by SARS-CoV at 30 h, while TNF-α, IFN-β and IP-10 induced by SARS-CoV were markedly higher than those induced by MERS-CoV at 24 and 30 h in infected Calu-3 cells. The activation of IL-8 and attenuated IFN-β response by MERS-CoV were also confirmed by protein measurements in the culture supernatant when compared to SARS-CoV and Sendai virus. To further confirm the attenuated antiviral response, cytokine response was compared to HCoV-229E in embryonal lung fibroblast, HFL, cells, which also revealed higher IFN-β and IP-10 levels induced by HCoV-229E than MERS-CoV at 24 and 30 h. While our data supported recent findings that MERS-CoV elicits attenuated innate immunity, this represents the first report to demonstrate delayed proinflammatory cytokine induction by MERS-CoV. Our results provide insights into the pathogenesis and treatment of MERS-CoV infections.
KEYWORDS: 229E, MERS, SARS, coronavirus, human
PMID: 24077366 [PubMed - as supplied by publisher]
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