我國科研人員聯合發文：精氨酸缺乏與發熱伴血小板減少綜合征有關

導言

SFTS病毒（發熱伴血小板減少綜合征病毒）是一種新型的布尼亞病毒科白蛉病毒屬病毒，因其引起嚴重發熱伴血小板減少綜合征而命名。該病毒是2010年首次在我國被發現，主要因為蜱蟲叮咬傳播。由於是新發現病毒，因此對該病毒的發病機制以及臨床干預手段還很少。而SFTS病毒又可通過基因突變、重組和在蜱媒介及脊椎動物宿主內進行同源性重組而快速進化，對人類造成威脅。

近日，我國軍事醫學科學院病原微生物生物安全國家重點實驗室，清華大學醫學院，山東大學等處的研究人員在國際著名學術期刊「Science Translational Medicine」發表了題為「Arginine deficiency is involved in thrombocytopenia and immunosuppression in severe fever with thrombocytopenia syndrome」的研究論文。該研究在醫院環境中進行了一項觀察性研究,研究人員對46名SFTS患者的血液進行了分析，結果他們發現病人體內的精氨酸（一種氨基酸）水平低下，與血小板計數低及免疫抑制有關，研究認為在SFTS病毒感染早期，體內精氨酸水平低下的患者更可能死亡。這些發現為SFTS的基礎發病機制提供了重要信息。研究人員隨後進行了隨機對照臨床試驗以補充精氨酸患者，結果發現接受精氨酸的患者血小板活性降低並出現了更快的病毒清除率。本研究結果或許意味著精氨酸可以成為治療SFTS及類似病毒性疾病的合適靶標，為更好地認識和治療SFTS病毒鋪平了道路。

部分結果速覽

Abstract：

Severe fever with thrombocytopenia syndrome (SFTS) caused by arecently identified bunyavirus, SFTSV, is an emerging infectious disease with extensive geographical distribution and high mortality. Progressive viral replication and severe thrombocytopenia are key features of SFTSV infection and fatal outcome, whereas the underlying mechanisms are unknown. We revealed arginine deficiency in SFTS cases by performing metabolomics analysis on two independent patient cohorts, suggesting that arginine metabolism by nitric oxide synthase and arginase is a key pathway in SFTSV infection and consequential death. Arginine deficiency was associated with decreased intraplatelet nitric oxide (Plt-NO) concentration, platelet activation, and thrombocytopenia. An expansion of arginase-expressing granulocytic myeloid-derived suppressor cells was observed, which was related to T cell CD3-ζ chain down-regulation and virus clearance disturbance, implicating a role of arginase activity and arginine depletion in the impaired anti-SFTSV T cell function. Moreover, a comprehensive measurement of arginine bioavailability, global arginine bioavailability ratio, was shown to be a good prognostic marker for fatal prediction in early infection. A randomized controlled trial demonstrated that arginine administration was correlated with enhanced Plt-NO concentration, suppressed platelet activation, and elevated CD3-ζ chain expression and eventually associated with an accelerated virus clearance and thrombocytopenia recovery. Together, our findings revealed the arginine catabolism pathway–associated regulation of platelet homeostasis and T cell dysregulation after SFTSV infection, which not only provided a functional mechanism underlying SFTS pathogenesis but also offered an alternative therapy choice for SFTS.

DOI:10.1126/scitranslmed.aat4162

本期編輯：vetjamie

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