BACKGROUND Endemic outbreaks of hantaviruses pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS) in humans. Using comparative genomic analyses of partial and nearly complete sequences of HTNV from humans and rodents, we were able to localize, with limitations, the putative infection locations for HFRS patients. Partial sequences might not reflect precise phylogenetic positions over the whole-genome sequences; finer granularity of rodent sampling reflects more precisely the circulation of strains. METHODS Five HFRS specimens were collected. Epidemiological surveys were conducted with the patients during hospitalization. We conducted active surveillance at suspected HFRS outbreak areas. We performed multiplex polymerase chain reaction-based next-generation sequencing to obtain the genomic sequence of HTNV from patients and rodents. The phylogeny of human- and rodent-derived HTNV was generated using the maximum likelihood method. For phylogeographic analyses, the tracing of HTNV genomes from HFRS patients was defined on the bases of epidemiological interviews, phylogenetic patterns of the viruses, and geographic locations of HTNV-positive rodents. RESULTS The phylogeographic analyses demonstrated genetic clusters of HTNV strains from clinical specimens, with HTNV circulating in rodents at suspected sites of patient infections. CONCLUSIONS This study demonstrates a major shift in molecular epidemiological surveillance of HTNV. Active targeted surveillance was performed at sites of suspected infections, allowing the high-resolution phylogeographic analysis to reveal the site of emergence of HTNV. We posit that this novel approach will make it possible to identify infectious sources, perform disease risk assessment, and implement preparedness against vector-borne viruses.

中文翻译：

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主动有针对性的监视，以识别汉坦病毒的出现部位。

背景技术汉坦病毒的地方性爆发在全球范围内构成了严重的公共健康威胁。汉坦病毒原体病毒（HTNV）会导致人类肾综合征（HFRS）出血热。通过对来自人类和啮齿类动物的HTNV的部分和几乎完整序列进行比较基因组分析，我们能够有限地定位HFRS患者的假定感染部位。部分序列可能无法反映出全基因组序列上精确的系统发育位置。啮齿动物采样的更细粒度更准确地反映了菌株的循环。方法收集5份HFRS标本。在住院期间对患者进行了流行病学调查。我们在疑似HFRS爆发地区进行了主动监视。我们进行了基于多重聚合酶链反应的下一代测序，从患者和啮齿动物中获得了HTNV的基因组序列。人类和啮齿动物衍生的HTNV的系统发育是使用最大似然法生成的。对于系统地理学分析，根据流行病学访谈，病毒的系统发育模式以及HTNV阳性啮齿动物的地理位置，确定了HFRS患者的HTNV基因组的轨迹。结果生理学分析表明，临床样本中的HTNV菌株具有遗传簇，HTNV在可疑患者感染部位的啮齿动物中循环。结论这项研究证明了HTNV分子流行病学监测的重大转变。在疑似感染的地点进行了有针对性的主动监视，使高分辨率的系统地理分析能够揭示HTNV的出现部位。我们认为，这种新颖的方法将使识别传染源，进行疾病风险评估以及对媒介传播的病毒做好准备成为可能。