Institute of Medical Virology, Helmut-Ruska-Haus, Charité Medical School, Berlin, Germany; Division of Virology, Labor Berlin Charité-Vivantes GmbH, Berlin, Germany.
Clin Microbiol Infect. 2014 Oct;20(10):O648-55. doi: 10.1111/1469-0691.12543. Epub 2014 Feb 20.
Members of the Dobrava-Belgrade virus (DOBV) species are hantaviruses carried by different Apodemus mice as reservoir hosts and causing haemorrhagic fever with renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, Apodemus agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (north and northeast Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The virus neutralization assay allowed a reliable identification of DOBV antibodies during both acute and convalescent phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAaemia seems to be short. Nucleotide sequences were amplified from four patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient-derived and A. agrarius-derived virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by the DOBV genotypes Dobrava or Sochi, all available data showed a mild clinical course of HFRS caused by DOBV-Kurkino infection without lethal outcomes.
多布拉瓦-贝尔格莱德病毒（DOBV）种属的病毒由不同的田鼠作为储存宿主携带，可导致人类发生肾综合征出血热（HFRS）。在中欧，与黄胸鼠（Apodemus agrarius）相关的 DOBV Kurkino 基因型较为流行。本文首次对中欧 DOBV-Kurkino 感染的血清学和分子诊断学、流行病学和临床特征进行了广泛研究。分析了居住在黄胸鼠栖息地（德国北部和东北部）且有发热症状的 570 名德国患者的血清样本。所有样本均通过 ELISA 进行检测，部分样本还通过免疫印迹、中和试验和 RT-PCR 进行了分析。确认 86 例患者感染了 DOBV。病毒中和试验可在感染的急性期和恢复期可靠地鉴定出 DOBV 抗体。然而，通过中和试验无法区分相关的 DOBV 基因型，需要进行分子分析。虽然 DOBV IgM 抗体在受感染的机体中持续存在，但 RNA 血症似乎较为短暂。从 4 名患者中扩增出了核苷酸序列，其分析结果表明感染了 DOBV-Kurkino。根据初步结果，当地患者和黄胸鼠衍生病毒序列的高度同源性可能有助于更准确地确定人类感染发生的地理地点。与由 DOBV 基因型 Dobrava 或 Sochi 引起的中度/重度 HFRS 不同，所有可用数据均表明 DOBV-Kurkino 感染引起的 HFRS 临床病程较轻，无致死结局。
