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[肠道病毒71型毒株热适应性进化过程中的毒力变异研究]

[Investigation of Virulence Variation of Enterovirus 71 Strains during Thermal Adaptive Evolution].

作者信息

Chen Heng, Cheng Yue, Meng Jian-Tong, Huang Wei-Wei, Huang Wei, Chen Zhen-Hua, Zhang Xiao-Chun, Yuan Qi-Wu, Wang Xi-Xi

机构信息

Chengdu Workstation for Emerging Infectious Disease Control and Prevention, Chinese Academy of Medical Sciences, Chengdu 610041, China.

Chengdu Center for Disease Control and Prevention, Chengdu 610041, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2022 May;53(3):409-413. doi: 10.12182/20220560104.

Abstract

OBJECTIVE

To study the virulence variation of enterovirus 71 (EV71) during thermal adaptive evolution, providing references for the prevention and control of the EV71-related hand, foot and mouth disease.

METHODS

Parental strains and thermal-adapted strains originating from EV71 sibling strains (lineage #100 and #101) were used for plaque assay validation, CCK-8 cytotoxicity experiment, and host proteomics studies after Vero cell infection. Plaque morphology and cell inhibition rate of the viral strains were obtained. Mass spectrometry was used to examine and analyze the functions of proteins that were differential expressed in the host cells.

RESULTS

Plaque morphology variation was found only in the heat-adapted strain of lineage #101. Increase in cell inhibition rate was observed in all the thermal-adapted strains, but the amount of increase varied in different strains. According to the results of clustering analysis and principal component analysis, after infection of Vero cells, the host cell protein profile of the heat-adapted strains was similar to that of the parental strains and the host cell protein profile of cold-adapted strains was similar to that of cell-adapted strains. It showed that 500 kinds of proteins presented inter-group difference in their expression, with 239 kinds being up-regulated proteins and 261 being down-regulated. The function of the up-regulated proteins were related to post-translational protein modification, while the functions of the down-regulated proteins were related to SRP-dependent cotranslational protein translocation/targeting to membrane and retrograde protein transport.

CONCLUSION

Virulence variations of enterovirus 71 may accompany thermal adaptive evolution, but its mechanism of action still awaits further investigation.

摘要

目的

研究肠道病毒71型(EV71)在热适应性进化过程中的毒力变异情况,为防控EV71相关手足口病提供参考依据。

方法

采用源自EV71同源株(谱系#100和#101)的亲代毒株和热适应毒株,进行蚀斑试验验证、CCK-8细胞毒性实验以及Vero细胞感染后的宿主蛋白质组学研究。获取病毒株的蚀斑形态和细胞抑制率。运用质谱技术检测和分析宿主细胞中差异表达蛋白质的功能。

结果

仅在谱系#101的热适应毒株中发现蚀斑形态变异。所有热适应毒株的细胞抑制率均有所增加,但不同毒株的增加幅度有所不同。根据聚类分析和主成分分析结果,Vero细胞感染后,热适应毒株的宿主细胞蛋白质谱与亲代毒株相似,冷适应毒株的宿主细胞蛋白质谱与细胞适应毒株相似。结果显示,有500种蛋白质在组间表达存在差异,其中239种为上调蛋白,261种为下调蛋白。上调蛋白的功能与蛋白质翻译后修饰相关,而下调蛋白的功能与SRP依赖的共翻译蛋白质转运/靶向膜以及逆行蛋白质转运有关。

结论

肠道病毒71型的毒力变异可能伴随热适应性进化,但其作用机制仍有待进一步研究。

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