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一种与人类发热疾病相关的新型 Orthonairovirus。

A New Orthonairovirus Associated with Human Febrile Illness.

机构信息

From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology (X.-A.Z., Y.-D.M., Y.-F.Z., Z.-Y.H., J.-T.Z., S.H., G.W., S.L., X.W., L.Z., G.-Q.S., C.P., R.W., H.-H.G., B.-G.J., H.L., W.L.), and the Institute of Medical Prevention and Control of Public Health Emergencies, Characteristic Medical Center of the Chinese People's Armed Police Force (F.T.), Beijing, Changchun Institute of Veterinary Medicine, Chinese Academy of Agricultural Sciences, Changchun (Y.-D.M., N.L., C.L.), the School of Public Health, Anhui Medical University, Hefei (Z.-Y.H., X.W., H.L., W.L.), Medical Detachment of Inner Mongolia Autonomous Region Forest Fire Brigade Daxing'anling Branch, Yakeshi (W.-J.L.), the First Affiliated Hospital of Jinzhou Medical University, Jinzhou (H.-X.Y.), Dandong Infectious Disease Hospital, Dandong (J.-Q.Z.), and the Center for Disease Control and Prevention in Zhalainuoer District, Hulunbuir (L.-F.J.) - all in China.

出版信息

N Engl J Med. 2024 Sep 5;391(9):821-831. doi: 10.1056/NEJMoa2313722.

DOI:10.1056/NEJMoa2313722
PMID:39231344
Abstract

BACKGROUND

In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV).

METHODS

We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models.

RESULTS

WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors () sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The tick is a possible vector that can transovarially transmit WELV.

CONCLUSIONS

A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).

摘要

背景

2019 年 6 月,一名患者在内蒙湿地公园被蜱虫叮咬后出现持续发热和多器官功能障碍。对该患者进行的下一代测序显示,其感染了一种以前未知的正呼肠孤病毒,我们将其命名为湿地病毒(WELV)。

方法

我们开展了主动的医院监测,以确定有蜱虫叮咬史的发热患者中 WELV 感染的流行率。进行了流行病学调查。分离出病毒,并在动物模型中研究了其感染性和致病性。

结果

WELV 是呼肠孤病毒科正呼肠孤病毒属的成员,与蜱传的 Hazara 正呼肠孤病毒基因群关系最为密切。通过逆转录-聚合酶链反应检测,在中国内蒙古、黑龙江、吉林和辽宁的 17 名患者中鉴定出急性 WELV 感染。这些患者表现为非特异性症状,包括发热、头晕、头痛、不适、肌痛、关节炎和背痛,较少出现瘀点和局部淋巴结病。有 1 名患者出现神经系统症状。常见的实验室发现包括白细胞减少、血小板减少以及 d-二聚体和乳酸脱氢酶水平升高。对 8 名患者恢复期样本的血清学评估显示,WELV 特异性抗体滴度比急性期样本高 4 倍。在在中国东北部采集的 5 种蜱虫以及绵羊、马、猪和 Transbaikal zokors()中检测到了 WELV RNA。从指数患者和蜱虫中分离出的病毒在人脐静脉内皮细胞中显示出细胞病变效应。腹腔内注射该病毒可导致 BALB/c、C57BL/6 和昆明小鼠致死性感染。蜱虫可能是可以经卵传递 WELV 的传播媒介。

结论

在中国东北部发现了一种新发现的正呼肠孤病毒,该病毒与人类发热疾病有关。(由国家自然科学基金和中国医学科学院创新基金医学科学资助)。

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