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柯萨奇病毒 B3MKP 株引起心肌炎的全基因组序列及其分子系统进化分析。

The whole genome sequence of coxsackievirus B3 MKP strain leading to myocarditis and its molecular phylogenetic analysis.

机构信息

Cardiovascular disease center, First Hospital of Jilin University, Changchun, Jilin 130021, China.

出版信息

Virol J. 2014 Feb 21;11:33. doi: 10.1186/1743-422X-11-33.

Abstract

BACKGROUND

In recent years, the reported infection cases by coxsackievirus (CV) have been on the rise. In order to reveal the relationship between the nucleotide and amino acid sequences and the viral virulence of the CVB3/MKP strain causing myocarditis, we initially confirmed the virulence of the strain in myocardial tissue and then carried out the whole genome sequencing of CVB3/MKP strain and performed a phylogenetic analysis among different CVB3 strains.

METHODS

CVB3/MKP infected mouse model was established to check lesions of myocardial tissue in mice using immunohistochemical detection at different periods. RT-PCR analysis was used to amplify seven fragments covering the whole viral sequence and comparable analysis was performed.

RESULTS

The immunohistochemical results showed that particles of CVB3/MKP virus persisted in the cardiac tissue and caused severe pathology. The length of whole genome sequence of CVB3/MKP strain was 7400 bp. CVB3/MKP had 99.7% and 99.6% homology in nucleotide sequence with CVB3/28 and non-virulent CVB3/0, respectively. The former can induce pancreatitis and myocarditis. The nucleotide sequence in the 5'untranslated region of CVB3/MKP strain shared 99.6% and 99.5% homology with CVB3/20 and CVB3/Nancy, respectively.

CONCLUSION

We confirmed in our animal experiments that CVB3/MKP had cardiotoxicity. CVB3/MKP, CVB3/28, and CVB3/0 may share evolutionary convergence and the 5'untranslated region (5'UTR) may be associated with virulence phenotype. Our findings will provide a basis for identifying the genomic determinant of viral virulence of CVB3/MKP strain and phylogenetic relationship among different CVB3 strains.

摘要

背景

近年来,柯萨奇病毒(CV)的报道感染病例呈上升趋势。为了揭示导致心肌炎的 CVB3/MKP 株的核苷酸和氨基酸序列与病毒毒力之间的关系,我们首先确定了该菌株在心肌组织中的毒力,然后对 CVB3/MKP 株进行了全基因组测序,并对不同 CVB3 株进行了系统进化分析。

方法

建立 CVB3/MKP 感染小鼠模型,在不同时期用免疫组化检测法检查小鼠心肌组织病变。采用 RT-PCR 扩增法扩增覆盖整个病毒序列的 7 个片段,并进行比较分析。

结果

免疫组化结果显示,CVB3/MKP 病毒颗粒持续存在于心脏组织中,并引起严重的病理变化。CVB3/MKP 株全基因组序列长度为 7400bp。CVB3/MKP 株与 CVB3/28 株和非致弱 CVB3/0 株的核苷酸序列同源性分别为 99.7%和 99.6%。前者可诱导胰腺炎和心肌炎。CVB3/MKP 株 5'非翻译区的核苷酸序列与 CVB3/20 株和 CVB3/Nancy 株分别有 99.6%和 99.5%的同源性。

结论

我们在动物实验中证实 CVB3/MKP 具有心脏毒性。CVB3/MKP、CVB3/28 和 CVB3/0 株可能具有进化趋同,5'非翻译区(5'UTR)可能与毒力表型有关。我们的研究结果将为鉴定 CVB3/MKP 株病毒毒力的基因组决定因素以及不同 CVB3 株之间的系统进化关系提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7978/3996064/db3f1d7543a7/1743-422X-11-33-1.jpg

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