Genetic Diversity and Reassortment of Hantaan Virus Tripartite RNA Genomes in Nature, the Republic of Korea.

Genetic Diversity and Reassortment of Hantaan Virus Tripartite RNA Genomes in Nature, the Republic of Korea.
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韩国共和国自然界中的遗传多样性和汉塔病毒三方RNA基因组的遗传多样性和重新分类。

DOI:
10.1371/journal.pntd.0004650
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发表时间:
2016-06
影响因子:
3.8
通讯作者:
Song JW
Song JW
中科院分区:
医学2区
文献类型:
--
作者:
Kim JA;Kim WK;No JS;Lee SH;Lee SY;Kim JH;Kho JH;Lee D;Song DH;Gu SH;Jeong ST;Park MS;Kim HC;Klein TA;Song JW

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汉坦病毒(HTNV)是一种阴性意义的布尼亚病毒科三核糖核酸病毒,是韩国最流行的汉坦病毒。它是人类肾综合征出血热(HFRS)的病原体,并在条纹田鼠黑线姬鼠(主要人畜共患宿主)中维持。临床HFRS病例在京畿道HFRS流行地区普遍报告。最近,一名来自江原道的韩国军人因感染HFRS而死亡,这促使人们对位于南北非武装地带(dmz)的江原道和京畿道的汉坦病毒流行病学和分布进行调查。为了阐明HTNV的地理分布和分子多样性,我们从2003-2014年捕获的黑线姬鼠肺组织中获取了HTNV大(L)、中(M)和小(S)片段的全基因组序列。与疾病管理本部确定的HFRS临床发病率一致,江原道自然感染小鼠的HTNV患病率低于京畿道。鉴定了34株HTNV病毒的全基因组序列,系统发育分析显示该病毒在有限地区具有地理多样性。重配分析首次表明HTNV基因组在韩国自然界中存在遗传交换。这项研究是首次证实HTNV在江原道分子流行的报告。HTNV的全基因组测序结果显示,韩国北部地区HTNV的地理谱系和分子多样性得到了很好的支持,这是由于HTNV基因组的自然重排。这些观察结果有助于更好地了解汉坦病毒的遗传多样性和分子进化。此外,HTNV三部分全基因组将为汉坦病毒感染时空暴发的系统地理分析提供数据库。肾综合征出血热(HFRS)和汉坦病毒肺综合征(HPS)是由汉坦病毒引起的流行性人畜共患传染病,属于布尼亚病毒科,含有负义三部分RNA基因组。汉坦病毒构成了一个新出现的重大公共卫生威胁,全世界每年报告的临床病例多达20万例,病死率为1-36%。在人类中,汉坦病毒传播的疾病是通过吸入从啮齿动物排泄物中雾化的病毒而感染的。然而,目前还没有有效的治疗方法或疫苗来预防这种疾病。从在韩国hfrs流行地区捕获的黑线姬鼠肺组织中获得了汉坦病毒(HTNV)全基因组序列。系统发育分析表明,HTNV三部分基因组序列在地理上聚集,表明HTNV在整个调查地区具有广泛的多样性。重配分析首先表明HTNV基因交换在韩国自然发生。这些观察结果有助于更好地了解hfrs流行地区汉坦病毒的遗传多样性和分子进化。HTNV基因组的完整序列将为地方性汉坦病毒传播疾病的系统地理分析和监测提供数据库。
Hantaan virus (HTNV), a negative sense tripartite RNA virus of the Family Bunyaviridae, is the most prevalent hantavirus in the Republic of Korea (ROK). It is the causative agent of Hemorrhagic Fever with Renal Syndrome (HFRS) in humans and maintained in the striped field mouse, Apodemus agrarius, the primary zoonotic host. Clinical HFRS cases have been reported commonly in HFRS-endemic areas of Gyeonggi province. Recently, the death of a member of the ROK military from Gangwon province due to HFRS prompted an investigation of the epidemiology and distribution of hantaviruses in Gangwon and Gyeonggi provinces that border the demilitarized zone separating North and South Korea. To elucidate the geographic distribution and molecular diversity of HTNV, whole genome sequences of HTNV Large (L), Medium (M), and Small (S) segments were acquired from lung tissues of A. agrarius captured from 2003–2014. Consistent with the clinical incidence of HFRS established by the Korea Centers for Disease Control & Prevention (KCDC), the prevalence of HTNV in naturally infected mice in Gangwon province was lower than for Gyeonggi province. Whole genomic sequences of 34 HTNV strains were identified and a phylogenetic analysis showed geographic diversity of the virus in the limited areas. Reassortment analysis first suggested an occurrence of genetic exchange of HTNV genomes in nature, ROK. This study is the first report to demonstrate the molecular prevalence of HTNV in Gangwon province. Whole genome sequencing of HTNV showed well-supported geographic lineages and the molecular diversity in the northern region of ROK due to a natural reassortment of HTNV genomes. These observations contribute to a better understanding of the genetic diversity and molecular evolution of hantaviruses. Also, the full-length of HTNV tripartite genomes will provide a database for phylogeographic analysis of spatial and temporal outbreaks of hantavirus infection. Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS) are endemic zoonotic infectious diseases caused by hantaviruses that belong to the Family Bunyaviridae containing negative-sense tripartite RNA genomes. Hantaviruses pose a critical emerging public health threat, with up to 200,000 clinical cases reported annually worldwide with 1–36% case fatality rates. In humans, hantavirus-borne diseases are contracted by the inhalation of viruses aerosolized from rodent excreta. However, there is no effective therapeutic or vaccine to prevent from the disease. Whole genome sequences of Hantaan virus (HTNV) were acquired from lung tissues of Apodemus agrarius captured in HFRS-endemic areas of the Republic of Korea (ROK). Phylogenetic analyses demonstrated that sequences of the HTNV tripartite genomes clustered geographically, showing broad diversity of HTNV throughout the areas surveyed. Reassortment analysis first suggested a natural occurrence of the HTNV genetic exchange in the ROK. These observations contribute to a better understanding of the genetic diversity and molecular evolution of hantaviruses in HFRS-endemic regions. The complete sequences of HTNV genomes will provide a database for the phylogeographic analysis and surveillance of endemic hantavirus-borne diseases.