Interferon and cytokine responses to SARS-coronavirus infection

Thiel, Volker; Weber, Friedemann

doi:10.1016/j.cytogfr.2008.01.001

Cited by 144 publications

(158 citation statements)

References 175 publications

(263 reference statements)

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“…Mice infected with the H1N1 virus were reported to exhibit different courses of ARDS and led to cytokine storm in the body (Garigliany et al, 2010). It is well known that cytokine storm plays a major role in pneumonia and ARDS (Thiel and Weber, 2008). The clinical study showed a slight increase of IL-6, IL-10 and TNF-α and high levels of IFN-γ and MCP-1 in patients with ARDS caused by H1N1 infection (Bermejo-Martin et al, 2009;Chen et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

The roots of Ilex asprella extract lessens acute respiratory distress syndrome in mice induced by influenza virus

Dai

et al. 2014

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 99%

The roots of Ilex asprella extract lessens acute respiratory distress syndrome in mice induced by influenza virus

Dai

et al. 2014

Journal of Ethnopharmacology

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“…The innate immune response is critical for host defence against respiratory coronaviruses (CoVs) (Charley et al , 2006; Frieman et al , 2008; Thiel & Weber, 2008). Most CoVs are sensitive to the antiviral effects of virus-induced IFN-α/β.…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, the group 1 CoVs in the family Coronaviridae , order Nidovirales , PRCV and transmissible gastroenteritis virus (TGEV) are potent IFN-α inducers (Charley et al , 2006; Van Reeth et al , 1999; Zhang et al , 2008). The recently identified human CoV, severe acute respiratory syndrome coronavirus (SARS)-CoV, which belongs to subgroup 2b of the group 2 CoVs (Kuiken et al , 2003; Lau et al , 2005; Saif, 2004), also elicits type I interferons (IFNs), but it may also evade their antiviral activity (Frieman et al , 2008; Thiel & Weber, 2008). The innate immune responses of the host against respiratory viruses involve alveolar macrophages, pulmonary epithelial cells, natural killer (NK) cells, dendritic cells and IFN-α/β responses in the lung.…”

Section: Introductionmentioning

confidence: 99%

Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections

Jung

Renukaradhya

Alekseev

et al. 2009

Journal of General Virology

101

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The innate immune response is critical for host defence against respiratory coronaviruses (CoVs). This study demonstrated that an ongoing respiratory virus infection compromises innate immune responses and affects the pathogenesis of a respiratory CoV co-infection. An innate immunosuppressive respiratory virus infection was established by infecting weaned pigs with porcine reproductive and respiratory syndrome virus (PRRSV); 10 days later, the pigs were exposed to porcine respiratory coronavirus (PRCV). The PRRSV/PRCV dual-infected pigs had reduced weight gains, a higher incidence of fever and more severe pneumonia compared with either single infection. Significant suppression of innate immune responses [reduced alpha interferon (IFN-a) levels in the lungs and reduced blood natural killer cell cytotoxicity] by the ongoing PRRSV infection was observed in dual-infected pigs, which coincided with exacerbated pneumonia during early PRCV infection. The subsequent PRCV infection led to enhanced PRRSV replication in the lungs and a trend towards increased serum T-helper type 1 (Th1) (IFN-c) but decreased Th2 [interleukin (IL)-4] responses, further exacerbating PRRSV pneumonia. Following PRCV infection, more severe PRRSV-related pulmonary alveolar macrophage (PAM) apoptosis occurred, as determined by an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay, suggesting increased PRRSV replication in PAMs. Collectively, these observations suggest interactive effects between PRCV and PRRSV via early innate (IFN-a) and later adaptive Th1 (IFN-c) and Th2 (IL-4) immune responses. These findings imply that an existing immunomodulating respiratory viral co-infection may be a contributing factor to more severe pneumonia in respiratory CoV disease. This study provides new insights into host-pathogen interactions related to co-infection by CoVs and other respiratory viruses.

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“…The production and action of type I interferons, which are major components of antiviral innate immunity (2,3), are inhibited at multiple levels by SARS coronavirus (4,5). This inhibition is thought to be mediated through viral structural and nonstructural proteins N, ORF3b, ORF6, nsp1, and papain-like protease (6 -12).…”

mentioning

confidence: 99%

Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex

Siu¹,

Kok²,

Ng³

et al. 2009

Journal of Biological Chemistry

263

311

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Severe acute respiratory syndrome (SARS) coronavirus is highly pathogenic in humans and evades innate immunity at multiple levels. It has evolved various strategies to counteract the production and action of type I interferons, which mobilize the front-line defense against viral infection. In this study we demonstrate that SARS coronavirus M protein inhibits gene transcription of type I interferons. M protein potently antagonizes the activation of interferon-stimulated response elementdependent transcription by double-stranded RNA, RIG-I, MDA5, TBK1, IKK⑀, and virus-induced signaling adaptor (VISA) but has no influence on the transcriptional activity of this element when IRF3 or IRF7 is overexpressed. M protein physically associates with RIG-I, TBK1, IKK⑀, and TRAF3 and likely sequesters some of them in membrane-associated cytoplasmic compartments. Consequently, the expression of M protein prevents the formation of TRAF3⅐TANK⅐TBK1/IKK⑀ complex and thereby inhibits TBK1/IKK⑀-dependent activation of IRF3/IRF7 transcription factors. Taken together, our findings reveal a new mechanism by which SARS coronavirus circumvents the production of type I interferons. Severe acute respiratory syndrome (SARS)2 coronavirus causes a highly lethal infectious disease in humans characterized by an aberrant immune response (1). The production and action of type I interferons, which are major components of antiviral innate immunity (2, 3), are inhibited at multiple levels by SARS coronavirus (4, 5). This inhibition is thought to be mediated through viral structural and nonstructural proteins N, ORF3b, ORF6, nsp1, and papain-like protease (6 -12).The signaling pathways through which viruses induce the production of type I interferons have been well characterized (13)(14)(15). In response to double-stranded RNA (dsRNA) produced during viral replication, endosomal Toll-like receptor 3 (TLR3) and cytoplasmic retinoic acid-inducible gene I (RIG-I) trigger the activation of two different pathways adapted to downstream kinases through TRIF (TLR adaptor inducing interferon ␤) and VISA, respectively. These pathways converge on the formation of TRAF3⅐TANK⅐TBK1/IKK⑀ complex, which catalyzes the phosphorylation of IRF3 and IRF7 transcription factors, leading to the activation of type I interferon promoters (15-17).SARS coronaviral proteins counteract the production of type I interferons at multiple steps. Although IRF3 phosphorylation was inhibited in cells expressing ORF3b, ORF6, or N protein (7), papain-like protease could physically interact with IRF3 and prevent its phosphorylation and nuclear translocation in a protease-independent manner (11). In addition, nsp1 suppressed the synthesis of host proteins including interferons by inducing mRNA degradation (6, 12). Meanwhile, viral proteins such as nsp1 and ORF6 were multifunctional (10,18,19) and could also inhibit interferon signaling. For example, both nsp1 and ORF6 inhibited the activity of STAT1, a key regulator of interferon-responsive genes (8, 9). Whereas nsp1 attenuated phosphorylati...

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Interferon and cytokine responses to SARS-coronavirus infection

Cited by 144 publications

References 175 publications

The roots of Ilex asprella extract lessens acute respiratory distress syndrome in mice induced by influenza virus

The roots of Ilex asprella extract lessens acute respiratory distress syndrome in mice induced by influenza virus

Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections

Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex

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