军事科学院军事医学研究院微生物流行病研究所曹务春研...

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蜱媒传染病是一类经蜱传播的自然疫源性疾病。从以前的“被忽视”到现在新疫区的“谈蜱色变”,蜱媒传染病的危害日益加大。近日，军事科学院军事医学研究院微生物流行病研究所曹务春研究团队发现了一种新的蜱传病毒病，相关研究结果发表在Lancet子刊EBioMedicine杂志，文章题目为Emergence of Human Infection with Jingmen Tick Virus in China: A Retrospective Study。EBioMedicine杂志同期配发评述文章。

Jingmen Tick Virus (JMTV)病毒最早在我国微小扇头蜱（Rhipicephalus microplus）等蜱种中被发现和命名。JMTV病毒分为四个节段，两个节段在进化地位上分别与黄病毒NS3，NS5片段最为接近，另两个节段与已知病毒序列都无同源性。JMTV在我国以及巴西、乌干达等地的蜱种或哺乳动物中被发现后，其对人是否致病一直未知。曹务春研究团队采用蜱细胞系BME/CTVM23成功分离了JMTV并实现稳定传代。发现该病毒实验室感染蜱后可以有效地在唾液腺复制，提示其可能通过叮咬传播。通过对蜱叮咬的病人皮肤组织高通量测序及RNA原位杂交，证实该病毒可以在皮肤局部复制，并且造成以中性粒细胞浸润为主的炎症反应。发现的4名病人以皮肤症状为主，有的伴淋巴结肿大。应用分离到的JMTV病毒，回顾性筛查哨点医院（牡丹江林业中心医院）蜱叮咬病人双份血清的特异性抗体反应，鉴定了8名患者恢复期血清JMTV抗体阳转。该8名患者症状较重，有1例出现严重的神经症状。分子生物学遗传进化分析发现，本研究鉴定的JMTV与以往报道的序列相比处于独立的分支，其他分支JMTV对人致病性值得进一步研究。


图1：JMTV病毒学特征及其在实验室感染蜱中的复制

图2：JMTV在病人皮肤组织中的复制及炎性细胞浸润

图3：JMTV四个片段分子生物学遗传进化分析

本研究丰富了科学界对新发蜱媒病原体感染谱、临床表现、病原学特征、自然疫源地特征等的认识，具有重要的公共卫生学意义，对临床医生鉴别诊断具有指导意义。军事科学院军事医学研究院微生物流行病研究所副研究员贾娜，博士生刘洪波，香港大学博士生倪雪冰，英国利物浦大学Lesley Bell-Sakyi教授为本文共同第一作者。曹务春研究员为本文通讯作者。本研究得到了国家自然科学基金项目，国家重点研发计划项目等的支持。

Abstract
Background A tick-borne segmented RNA virus called Jingmen tick virus (JMTV) was recently identified, variants of which were detected in a non-human primate host and fatal patients with Crimean-Congo haemorrhagic fever. We investigated its infectivity and pathogenicity for humans.
Methods We obtained skin-biopsy, blood and serum samples from patients with tick bites, and used high-throughput sequencing, in situ hybridisation, and serologic testing to diagnose and ascertain the cases of JMTV infection.
Findings A JMTV strain was isolated from the tick Amblyomma javanense into an embryo-derived tick cell line. We obtained sustained passage of JMTV, and revealed that it was able to accumulate in salivary glands of experimentally infected ticks. Four JMTV-infected patients were identified by high-throughput sequencing of skin biopsies and blood samples. The virus replication in skin tissue was visualised by in situ hybridisation. The four patients all had an itchy or painful eschar at the site of tick bite, with or without lymphadenopathy. Immunohistochemical examination revealed remarkable local inflammation manifested as infiltration by neutrophils. Eight patients were identified by serological testing and showed more severe clinical manifestations. Two Ixodes persulcatus ticks detached from patients were positive for JMTV. All JMTV strains identified in this study formed a well-supported sub-lineage, distinct from those previously reported in China.   
Interpretation The public significance of JMTV should be highly concerning due to its pathogenicity for humans and efficient transmission by potential ticks.
Fundings China Natural Science Foundation, China State Key Research Development Programme, and United Kingdom Biotechnology and Biological Sciences Research Council.  

原文链接：https://www.ebiomedicine.com/article/S2352-3964(19)30238-5/fulltext