Center for Disease Control and Prevention of Henan Province, Zhengzhou, China.
PLoS Pathog. 2011 Nov;7(11):e1002369. doi: 10.1371/journal.ppat.1002369. Epub 2011 Nov 17.
Since 2007, many cases of fever, thrombocytopenia and leukopenia syndrome (FTLS) have emerged in Henan Province, China. Patient reports of tick bites suggested that infection could contribute to FTLS. Many tick-transmitted microbial pathogens were tested for by PCR/RT-PCR and/or indirect immunofluorescence assay (IFA). However, only 8% (24/285) of samples collected from 2007 to 2010 tested positive for human granulocytic anaplasmosis (HGA), suggesting that other pathogens could be involved. Here, we used an unbiased metagenomic approach to screen and survey for microbes possibly associated with FTLS. BLASTx analysis of deduced protein sequences revealed that a novel bunyavirus (36% identity to Tehran virus, accession: HQ412604) was present only in sera from FTLS patients. A phylogenetic analysis further showed that, although closely related to Uukuniemi virus of the Phlebovirus genus, this virus was distinct. The candidate virus was examined for association with FTLS among samples collected from Henan province during 2007-2010. RT-PCR, viral cultures, and a seroepidemiologic survey were undertaken. RT-PCR results showed that 223 of 285 (78.24%) acute-phase serum samples contained viral RNA. Of 95 patients for whom paired acute and convalescent sera were available, 73 had serologic evidence of infection, with 52 seroconversions and 21 exhibiting a 4-fold increase in antibody titer to the virus. The new virus was isolated from patient acute-phase serum samples and named Henan Fever Virus (HNF virus). Whole-genome sequencing confirmed that the virus was a novel bunyavirus with genetic similarity to known bunyaviruses, and was most closely related to the Uukuniemi virus (34%, 24%, and 29% of maximum identity, respectively, for segment L, M, S at maximum query coverage). After the release of the GenBank sequences of SFTSV, we found that they were nearly identical (>99% identity). These results show that the novel bunyavirus (HNF virus) is strongly correlated with FTLS.
自 2007 年以来，中国河南省出现了多例发热、血小板减少和白细胞减少综合征（FTLS）病例。患者报告的蜱虫叮咬表明感染可能导致 FTLS。通过 PCR/RT-PCR 和/或间接免疫荧光测定（IFA）对许多蜱传微生物病原体进行了测试。然而，仅从 2007 年至 2010 年收集的 285 份样本中，有 8%（24/285）检测出人粒细胞无形体病（HGA）呈阳性，表明可能涉及其他病原体。在这里，我们使用无偏倚的宏基因组方法来筛选和检测可能与 FTLS 相关的微生物。推导的蛋白质序列的 BLASTx 分析表明，一种新型布尼亚病毒（与德黑兰病毒的 36% 同一性，登录号：HQ412604）仅存在于 FTLS 患者的血清中。系统发育分析进一步表明，尽管与 Phlebovirus 属的 Uukuniemi 病毒密切相关，但该病毒是不同的。在 2007 年至 2010 年期间从河南省采集的样本中，对候选病毒与 FTLS 的相关性进行了检测。进行了 RT-PCR、病毒培养和血清流行病学调查。RT-PCR 结果显示，285 份急性期血清样本中的 223 份含有病毒 RNA。在有配对急性期和恢复期血清的 95 名患者中，有 73 名有感染的血清学证据，52 名血清转换，21 名抗体滴度增加 4 倍。新病毒从患者急性期血清样本中分离出来，并命名为河南发热病毒（HNF 病毒）。全基因组测序证实该病毒是一种新型布尼亚病毒，与已知布尼亚病毒具有遗传相似性，与 Uukuniemi 病毒最为密切相关（最大查询覆盖率下分别为 L、M、S 片段的 34%、24%和 29%）。在 SFTSV 的 GenBank 序列发布后，我们发现它们几乎相同（>99%的同一性）。这些结果表明，新型布尼亚病毒（HNF 病毒）与 FTLS 密切相关。
