中山大学陈瑶生教授团队在PRRSV研究领域取得突破性成果
2017-05-15中国病毒学论坛
2017年5月10日，国际病毒学顶级期刊《Journal of Virology》在线发表了中山大学生命科学学院陈瑶生教授团队郭春和博士在PRRSV领域所取得的突破性成果“Heparanase upregulation contributes to porcine reproductive and respiratorysyndrome virus release”。
猪蓝耳病毒（PRRSV）主要感染肺泡巨噬细胞，破坏免疫系统，引起免疫抑制，对养猪业造成巨大损失，相当于人的艾滋病毒。目前该病毒致病机理还未完全阐述。
该团队郭春和博士一直致力于PRRSV研究。其在PRRSV感染不同时间点发现：病毒感染早期硫酸乙酰肝素（Heparan sulfate, HS）受体表达量升高，以促进病毒吸附；但是，在感染晚期，HS表达量下降，即病毒抑制HS表达。对此，郭博士展开详细研究，他发现PRRSV在感染晚期，病毒需要从细胞膜表面释放出来，而此时膜上的HS会与病毒相互黏连，抑制病毒释放，即HS受体是一把双刃剑。PRRSV为了释放出来，通过激活NF-κB信号通路上调表达乙酰肝素酶Heparanase，并通过激活组织蛋白酶Cathepsin L激活Heparanase，激活的Heparanase迁移到细胞膜上切割HS，抑制其与病毒粒子黏连，从而促进病毒释放（如下图所示）。
PRRSV释放模式图
本研究首次阐述了PRRSV释放机制，对该病毒防控具有重要指导意义。乙酰肝素酶Heparanase可作为抗PRRSV的重要靶位点。对此，郭春和博士挖掘到锌离子载体Pyrithione通过靶向Heparanase抑制病毒复制，相关研究成果已申报国家发明专利，并发表在中科院一区Veterinary Microbiology杂志上。
Heparanase upregulation contributes to porcine reproductive and respiratorysyndrome virus release
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV)continues to cause substantial economic losses to the pig industry worldwide.Heparan sulfate(HS) is used by PRRSV forinitial attachment to target cells. However, the role of HS in the latephase of PRRSV infectionand the mechanism of virus releasefrom host cells remain largely unknown. In this study, we showedthatPRRSV infection causeda decrease of HSexpressionand upregulated heparanase, the only known enzyme capable to degrade HS. We subsequently demonstrated thatthe NF-κBsignaling pathway and cathepsin Lprotease wereinvolved in regulation of PRRSV infection-inducedheparanase. In addition, we found that ablation of heparanase expression using small interfering RNA duplexes increased cell surface expression of HS and suppressed PRRSV replication and release, whereas overexpression of heparanase reduced HS surface expression and enhanced PRRSV replication and release.These data suggestthatPRRSV activates NF-κBand cathepsin L to upregulate and processheparanase, then the active heparanase cleave HS, resulting inviral release. Our findings provide new insight into the molecular mechanism of PRRSVegress from host cells, which mighthelp us tofurther understand PRRSV pathogenesis.
原文链接：http://jvi.asm.org/content/early/2017/05/04/JVI.00625-17.long
文章来源/中国病毒学论坛
作者/郭春和