Downregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome

Abstract Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease with high mortality and increasing prevalence in the East Asia. Though the etiological agent has been identified as a novel Bunyavirus, cellular mechanisms of viral pathogenesis and host immune response to...

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Autores principales:	Peixin Song, Nan Zheng, Li Zhang, Yong Liu, Taoyu Chen, Changjun Bao, Zhifeng Li, Wei Yong, Yongyang Zhang, Chao Wu, Zhiwei Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ccba8e6aba85462ba274ab3940c2849b
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spelling	oai:doaj.org-article:ccba8e6aba85462ba274ab3940c2849b2021-12-02T12:32:37ZDownregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome10.1038/s41598-017-06921-62045-2322https://doaj.org/article/ccba8e6aba85462ba274ab3940c2849b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06921-6https://doaj.org/toc/2045-2322Abstract Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease with high mortality and increasing prevalence in the East Asia. Though the etiological agent has been identified as a novel Bunyavirus, cellular mechanisms of viral pathogenesis and host immune response to SFTS virus infection remain unknown. A comprehensive study was conducted on a cohort of 70 patients on clinical manifestations, viral loads, modulation of cytokines, serum interferon level, immune related gene expression in peripheral blood cells, and dynamic changes of circulating dendritic cells during the acute phase of SFTSV infection. We found that high level viremia, reduced platelets, coagulation dysfunction, multi-organ injuries, elevated IL-6 and TNF-α were closely associated with the aggravation of SFTS. In addition, we demonstrated strong correlations between disease severity and the decline of serum IFN-β and IL-1β level, reduction of myeloid dendritic cells (mDCs) and suppressed Toll like receptor 3 expression in monocytes and mDCs. In general, dysfunction of innate immune response and cytokine storm are both involved in the pathogenesis of SFTS. Reduction of myeloid DCs contributes to the fatal outcome of SFTS virus infection, and the regulation of TLR3 could probably be the mechanism.Peixin SongNan ZhengLi ZhangYong LiuTaoyu ChenChangjun BaoZhifeng LiWei YongYongyang ZhangChao WuZhiwei WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Peixin Song Nan Zheng Li Zhang Yong Liu Taoyu Chen Changjun Bao Zhifeng Li Wei Yong Yongyang Zhang Chao Wu Zhiwei Wu Downregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome
description	Abstract Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease with high mortality and increasing prevalence in the East Asia. Though the etiological agent has been identified as a novel Bunyavirus, cellular mechanisms of viral pathogenesis and host immune response to SFTS virus infection remain unknown. A comprehensive study was conducted on a cohort of 70 patients on clinical manifestations, viral loads, modulation of cytokines, serum interferon level, immune related gene expression in peripheral blood cells, and dynamic changes of circulating dendritic cells during the acute phase of SFTSV infection. We found that high level viremia, reduced platelets, coagulation dysfunction, multi-organ injuries, elevated IL-6 and TNF-α were closely associated with the aggravation of SFTS. In addition, we demonstrated strong correlations between disease severity and the decline of serum IFN-β and IL-1β level, reduction of myeloid dendritic cells (mDCs) and suppressed Toll like receptor 3 expression in monocytes and mDCs. In general, dysfunction of innate immune response and cytokine storm are both involved in the pathogenesis of SFTS. Reduction of myeloid DCs contributes to the fatal outcome of SFTS virus infection, and the regulation of TLR3 could probably be the mechanism.
format	article
author	Peixin Song Nan Zheng Li Zhang Yong Liu Taoyu Chen Changjun Bao Zhifeng Li Wei Yong Yongyang Zhang Chao Wu Zhiwei Wu
author_facet	Peixin Song Nan Zheng Li Zhang Yong Liu Taoyu Chen Changjun Bao Zhifeng Li Wei Yong Yongyang Zhang Chao Wu Zhiwei Wu
author_sort	Peixin Song
title	Downregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome
title_short	Downregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome
title_full	Downregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome
title_fullStr	Downregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome
title_full_unstemmed	Downregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome
title_sort	downregulation of interferon-β and inhibition of tlr3 expression are associated with fatal outcome of severe fever with thrombocytopenia syndrome
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ccba8e6aba85462ba274ab3940c2849b
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Downregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome

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