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      Changes in peripheral blood cytokines in patients with severe fever with thrombocytopenia syndrome

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          Abstract

          Severe fever with thrombocytopenia syndrome (SFTS) is recognized as an emerging infectious disease. This study aimed to investigate the pathogenic mechanism of SFTS. A total of 100 subjects were randomly included in the study. Cytokine levels were detected by enzyme‐linked immunosorbent assay and the viral load was detected by micro drop digital PCR. The results showed that levels of interleukin‐6 (IL‐6), IL‐8, IL‐10, IFN‐inducible protein‐10 (IP‐10), monocyte chemoattractant protein‐1 (MCP‐1), macrophage inflammatory protein‐1α (MIP‐1α), transforming growth factor‐β1 (TGF‐β1), and regulated upon activation normal T cell expressed and secreted factor (RANTES) differed significantly among the SFTS patient group, healthy people group, and asymptomatic infection group ( p < .05). Compared to the healthy people group, the patient group had increased cytokine levels (IL‐6, IL‐10, IP‐10, MCP‐1, and IFN‐γ) but reduced levels of IL‐8, TGF‐β1, and RANTES ( p < .0167). IL‐6, IL‐8, IL‐10, IP‐10, MCP‐1, MIP‐1α, TGF‐β1, and the RANTES levels had different trends after the onset of the disease. IL‐6, IL‐10, IP‐10, and MCP‐1 levels in severe patients were higher than those in mild patients ( p < .05). There was a positive correlation between viral load and IL‐6 and IP‐10 but a negative correlation between viral load and RANTES. SFTSV could cause a cytokine change: the cytokine levels of patients had different degrees of fluctuation after the onset of the disease. The levels of IL‐6 and IL‐8 in the asymptomatic infection group were found between the SFTS patients group and the healthy people group. The levels of IL‐6, IL‐10, IP‐10, and MCP‐1 in the serum could reflect the severity of the disease, and the levels of IL‐6, IP‐10, and RANTES were correlated with the viral load.

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          Fever with thrombocytopenia associated with a novel bunyavirus in China.

          Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing. We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples. We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness. A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).
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            The cytokine storm of severe influenza and development of immunomodulatory therapy

            Severe influenza remains unusual in its virulence for humans. Complications or ultimately death arising from these infections are often associated with hyperinduction of proinflammatory cytokine production, which is also known as ‘cytokine storm'. For this disease, it has been proposed that immunomodulatory therapy may improve the outcome, with or without the combination of antiviral agents. Here, we review the current literature on how various effectors of the immune system initiate the cytokine storm and exacerbate pathological damage in hosts. We also review some of the current immunomodulatory strategies for the treatment of cytokine storms in severe influenza, including corticosteroids, peroxisome proliferator-activated receptor agonists, sphingosine-1-phosphate receptor 1 agonists, cyclooxygenase-2 inhibitors, antioxidants, anti-tumour-necrosis factor therapy, intravenous immunoglobulin therapy, statins, arbidol, herbs, and other potential therapeutic strategies.
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              CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications

              C–X–C motif chemokine 10 (CXCL10) also known as interferon γ-induced protein 10 kDa (IP-10) or small-inducible cytokine B10 is a cytokine belonging to the CXC chemokine family. CXCL10 binds CXCR3 receptor to induce chemotaxis, apoptosis, cell growth and angiostasis. Alterations in CXCL10 expression levels have been associated with inflammatory diseases including infectious diseases, immune dysfunction and tumor development. CXCL10 is also recognized as a biomarker that predicts severity of various diseases. A review of the emerging role of CXCL10 in pathogenesis of infectious diseases revealed diverse roles of CXCL10 in disease initiation and progression. The potential utilization of CXCL10 as a therapeutic target for infectious diseases is discussed.
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                Author and article information

                Contributors
                hxyzzu@163.com
                Journal
                J Med Virol
                J Med Virol
                10.1002/(ISSN)1096-9071
                JMV
                Journal of Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                0146-6615
                1096-9071
                11 March 2021
                August 2021
                : 93
                : 8 ( doiID: 10.1002/jmv.v93.8 )
                : 4704-4713
                Affiliations
                [ 1 ] Department of Infectious Disease Control and Prevention Henan Province Center for Disease Control and Prevention Zhengzhou China
                [ 2 ] College of Public Health, Zhengzhou University Zhengzhou China
                [ 3 ] Henan Key Laboratory of Pathogenic Microorganisms, Henan Province Center for Disease Control and Prevention Zhengzhou China
                [ 4 ] Health Policy Research Center Henan Academy of Medical Sciences Zhengzhou China
                Author notes
                [*] [* ] Correspondence Xueyong Huang, Department of Infectious Disease Control and Prevention, Henan Center for Disease Control and Prevention, No. 105 South Agricultural Rd, Zhengdong New District, 450016 Zhengzhou, China.

                Email: hxyzzu@ 123456163.com

                Author information
                http://orcid.org/0000-0001-8995-9274
                Article
                JMV26877
                10.1002/jmv.26877
                8360139
                33590892
                fbcf48f9-cf53-48b3-9b0d-62803d204318
                © 2021 The Authors. Journal of Medical Virology Published by Wiley Periodicals LLC

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 February 2021
                : 21 September 2020
                : 12 February 2021
                Page count
                Figures: 3, Tables: 3, Pages: 10, Words: 4816
                Funding
                Funded by: Henan Medical Science and Technology Program
                Award ID: 2018010029
                Award ID: 2018020510
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81573204
                Award ID: 81773500
                Funded by: Henan Young and Middle‐aged Health Science and Technology Innovation Leader Training Project
                Award ID: YXKC202006
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                August 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.5 mode:remove_FC converted:12.08.2021

                Microbiology & Virology
                asymptomatic infected persons,cytokines,patients,severe fever with thrombocytopenia syndrome,viral load

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