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普马拉病毒和多布拉瓦病毒在波斯尼亚和黑塞哥维那引发肾综合征出血热:早期患者血清中高度交叉中和抗体反应的证据。

Puumala and Dobrava viruses cause hemorrhagic fever with renal syndrome in Bosnia-Herzegovina: evidence of highly cross-neutralizing antibody responses in early patient sera.

作者信息

Lundkvist A, Hukic M, Hörling J, Gilljam M, Nichol S, Niklasson B

机构信息

Swedish Institute for Infectious Disease Control, Stockholm.

出版信息

J Med Virol. 1997 Sep;53(1):51-9.

PMID:9298732
Abstract

Hantavirus infection was diagnosed serologically by mu-capture IgM and IgG ELISAs in hemorrhagic fever with renal syndrome (HFRS) patients admitted to Tuzla Hospital, Bosnia-Herzegovina. The results indicated that more than one hantavirus caused the outbreak. To address the question of which hantavirus serotypes were involved, sequentially drawn sera were analyzed by focus reduction neutralization test (FRNT) for antibodies against Puumala, Hantaan, Dobrava, and Seoul hantaviruses. The data revealed that acute- or early convalescent-phase sera, even when drawn as late as 3 weeks after the onset of disease, could not be used for typing of the causative hantavirus; a significant number of these samples showed similar reactivity of neutralizing antibodies to several different hantavirus serotypes. Moreover, although several acute-phase sera showed the highest FRNT titer to Hantaan virus, convalescent sera from these patients in all cases showed high specificity for Puumala or Dobrava viruses. This phenomenon, interpreted as a cross-neutralizing primary antibody response, makes several earlier reports concerning causative agents of HFRS questionable. Serological examination of small rodents trapped in the endemic area identified Puumala- and Dobrava-like virus infections. RT-PCR and sequencing of rodent lung samples identified Dobrava virus in one yellow-necked field mouse (Apodemus flavicollis). Cross-FRNT data, using polyclonal rabbit antibodies, clearly confirmed Dobrava virus as a unique hantavirus serotype. In conclusion, the results revealed that both Puumala- and Dobrava-like viruses caused HFRS in Bosnia-Herzegovina, whereas no signs of Hantaan or Seoul virus involvement were found.

摘要

在波斯尼亚和黑塞哥维那图兹拉医院收治的肾综合征出血热(HFRS)患者中,通过μ捕获IgM和IgG酶联免疫吸附测定(ELISA)对汉坦病毒感染进行血清学诊断。结果表明,不止一种汉坦病毒导致了此次疫情爆发。为了确定涉及哪些汉坦病毒血清型,通过蚀斑减少中和试验(FRNT)对连续采集的血清进行分析,以检测针对普马拉、汉滩、多布拉瓦和汉城汉坦病毒的抗体。数据显示,急性期或早期恢复期血清,即使在疾病发作后3周才采集,也不能用于对致病汉坦病毒进行分型;这些样本中有相当数量对几种不同汉坦病毒血清型显示出相似的中和抗体反应性。此外,尽管几份急性期血清对汉滩病毒显示出最高的FRNT滴度,但这些患者的恢复期血清在所有情况下对普马拉或多布拉瓦病毒都表现出高特异性。这种现象被解释为交叉中和的初级抗体反应,使得一些关于HFRS病原体的早期报告受到质疑。对在疫区捕获的小型啮齿动物进行血清学检查,发现了类似普马拉和多布拉瓦病毒的感染。对啮齿动物肺样本进行逆转录聚合酶链反应(RT-PCR)和测序,在一只黄颈姬鼠(Apodemus flavicollis)中鉴定出多布拉瓦病毒。使用多克隆兔抗体的交叉FRNT数据明确证实多布拉瓦病毒是一种独特的汉坦病毒血清型。总之,结果显示在波斯尼亚和黑塞哥维那,普马拉样病毒和多布拉瓦样病毒都导致了HFRS,而未发现汉滩病毒或汉城病毒感染的迹象。

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