Host Cytokine Storm Is Associated With Disease Severity of Severe Fever With Thrombocytopenia Syndrome

Sun, Yawang; Jin, Cong; Zhan, Faxian; Wang, Xianjun; Liang, Mifang; Zhang, Quanfu; Ding, Shujun; Guan, Xiaohong; Huo, Xixiang; Li, Chuan; Qu, Jing; Wang, Qin; Zhang, Shuo; Zhang, Yanping; Wang, Shiwen; Xu, Anqiang; Bi, Zhenqiang; Li, Dexin

doi:10.1093/infdis/jis452

Cited by 231 publications

(263 citation statements)

References 26 publications

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“…Since SFTSV is a leading public health issues, researches on its clinical characteristics, pathogenic mechanism, detection methods, and epidemiologic characteristics were conducted (6)(7)(8)(9)(10)(11)(12)(13). With regards to SFTSV epidemiology, seroprevalence of the healthy population in endemic areas has previously been investigated (14)(15)(16); however, in non-endemic areas, it is unclear, and more knowledge in this area is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Presence of Antibodies against Severe Fever with Thrombocytopenia Syndrome Virus in Non-Endemic Areas of China

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Presence of Antibodies against Severe Fever with Thrombocytopenia Syndrome Virus in Non-Endemic Areas of China

et al. 2017

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“…SFTSV infection results in high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, neural symptoms, and bleeding with high mortality rates of up to 30% (Yu et al, 2011;Gai et al, 2012). The severity of SFTS results from an infection-induced cytokine storm with abnormally expressed cytokine profi les Sun et al, 2012b). Up to 240 infections and 30 fatalities from SFTSV were reported in China in 2011 (Yu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation

et al. 2013

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Severe fever with thrombocytopenia syndrome virus (SFTSV), a member of the Phlebovirus genus from the Bunyaviridae family endemic to China, is the causative agent of life-threatening severe fever with thrombocytopenia syndrome (SFTS), which features high fever and hemorrhage. Similar to other negative-sense RNA viruses, SFTSV encodes a nucleocapsid protein (NP) that is essential for viral replication. NP facilitates viral RNA encapsidation and is responsible for the formation of ribonucleoprotein complex. However, recent studies have indicated that NP from Phlebovirus members behaves in inhomogeneous oligomerization states. In the present study, we report the crystal structure of SFTSV NP at 2.8 Å resolution and demonstrate the mechanism by which it processes a ringshaped hexameric form to accomplish RNA encapsidation. Key residues essential for oligomerization are identifi ed through mutational analysis and identifi ed to have a signifi cant impact on RNA binding, which suggests that correct formation of highly ordered oligomers is a critical step in RNA encapsidation. The fi ndings of this work provide new insights into the discovery of new antiviral reagents for Phlebovirus infection.

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“…Although SFTSV NSs has been shown to inhibit both NFkB and IRF3 transcription factors (Qu et al, 2012), we noted the upregulated expression of many NFkB-regulated cytokines such as IL-6, IL-8 and TNF-a in humans and primates infected with SFTSV (Deng et al, 2012;Sun et al, 2012;Jin et al, 2015). To resolve this discrepancy, we compared the impact of NSs expression on Sendai virus (SENV)-induced activation of IFN-b promoter and canonical kB elements.…”

mentioning

confidence: 97%

Suppression of type I and type III IFN signalling by NSs protein of severe fever with thrombocytopenia syndrome virus through inhibition of STAT1 phosphorylation and activation

Chaudhary

Zhang

Yuen

et al. 2015

Journal of General Virology

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Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen causing significant morbidity and mortality in Asia. NSs protein of SFTSV is known to perturb type I IFN induction and signalling, but the mechanism remains to be fully understood. Here, we showed the suppression of both type I and type III IFN signalling by SFTSV NSs protein is mediated through inhibition of STAT1 phosphorylation and activation. Infection with live SFTSV or expression of NSs potently suppressed IFN-stimulated genes but not NFkB activation. NSs was capable of counteracting the activity of IFN-a1, IFN-b, IFN-l1 and IFN-l2. Mechanistically, NSs associated with STAT1 and STAT2, mitigated IFN-b-induced phosphorylation of STAT1 at S727, and reduced the expression and activity of STAT1 protein in IFN-b-treated cells, resulting in the inhibition of STAT1 and STAT2 recruitment to IFNstimulated promoters. Taken together, SFTSV NSs protein is an IFN antagonist that suppresses phosphorylation and activation of STAT1.

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Host Cytokine Storm Is Associated With Disease Severity of Severe Fever With Thrombocytopenia Syndrome

Abstract: The study demonstrates that SFTSV infection induces a cytokine storm with abnormally expressed cytokine profiles, which are associated with the disease severity.

Cited by 231 publications

References 26 publications

Presence of Antibodies against Severe Fever with Thrombocytopenia Syndrome Virus in Non-Endemic Areas of China

Presence of Antibodies against Severe Fever with Thrombocytopenia Syndrome Virus in Non-Endemic Areas of China

The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation

Suppression of type I and type III IFN signalling by NSs protein of severe fever with thrombocytopenia syndrome virus through inhibition of STAT1 phosphorylation and activation

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