| Title | Arginine deficiency is involved in thrombocytopenia and immunosuppression in severe fever with thrombocytopenia syndrome |
| Authors | Li, Xiao-Kun Lu, Qing-Bin Chen, Wei-Wei Xu, Wen Liu, Rong Zhang, Shao-Fei Du, Juan Li, Hao Yao, Ke Zhai, Di Zhang, Pan-He Xing, Bo Cui, Ning Yang, Zhen-Dong Yuan, Chun Zhang, Xiao-Ai Xu, Zhe Cao, Wu-Chun Hu, Zeping Liu, Wei |
| Affiliation | Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, 20 Dongda St, Beijing 100071, Peoples R China. Peking Univ, Sch Publ Hlth, Dept Lab Sci & Technol, 38 Xueyuan Rd, Beijing 100191, Peoples R China. Peoples Liberat Army, Hosp 302, 100 West 4th Ring Rd, Beijing 100039, Peoples R China. Wuhan Univ, Sch Basic Med Sci, Sch Med, 185 Donghu St, Wuhan 430071, Hubei, Peoples R China. Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China. Peoples Liberat Army, Hosp 154, 104 Nan Hu Rd, Xinyang 464000, Peoples R China. Shandong Univ, Sch Publ Hlth, Jinan 250012, Shandong, Peoples R China. Beijing Key Lab Vector Borne & Nat Focus Infect D, Microbiol & Epidemiol, Beijing, Peoples R China. Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, 20 Dongda St, Beijing 100071, Peoples R China. Hu, ZP (reprint author), Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China. Cao, WC Liu, W (reprint author), Shandong Univ, Sch Publ Hlth, Jinan 250012, Shandong, Peoples R China. Liu, W (reprint author), Beijing Key Lab Vector Borne & Nat Focus Infect D, Microbiol & Epidemiol, Beijing, Peoples R China. |
| Keywords | NITRIC-OXIDE VIRUS-INFECTION SUPPRESSOR-CELLS PLATELET ACTIVATION DISEASE METABOLISM CHINA RESPONSES BIOAVAILABILITY EPIDEMIOLOGY |
| Issue Date | 2018 |
| Publisher | SCIENCE TRANSLATIONAL MEDICINE |
| Citation | SCIENCE TRANSLATIONAL MEDICINE. 2018, 10(459). |
| Abstract | Severe fever with thrombocytopenia syndrome (SFTS) caused by a recently 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-zeta 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-zeta 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. |
| URI | http://hdl.handle.net/20.500.11897/517269 |
| ISSN | 1946-6234 |
| DOI | 10.1126/scitranslmed.aat4162 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 公共卫生学院 |
