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2017年5月10日，國(guó)際病毒學(xué)頂級(jí)期刊《Journal of Virology》在線發(fā)表了中山大學(xué)生命科學(xué)學(xué)院陳瑤生教授團(tuán)隊(duì)郭春和博士在PRRSV領(lǐng)域所取得的突破性成果“Heparanase upregulation contributes to porcine reproductive and respiratory syndrome virus release”。

豬藍(lán)耳病毒（PRRSV）主要感染肺泡巨噬細(xì)胞，破壞免疫系統(tǒng)，引起免疫抑制，對(duì)養(yǎng)豬業(yè)造成巨大損失，相當(dāng)于人的艾滋病毒。目前該病毒致病機(jī)理還未完全闡述。

該團(tuán)隊(duì)郭春和博士一直致力于PRRSV研究。其在PRRSV感染不同時(shí)間點(diǎn)發(fā)現(xiàn)：病毒感染早期硫酸乙酰肝素（Heparan sulfate, HS）受體表達(dá)量升高，以促進(jìn)病毒吸附；但是，在感染晚期，HS表達(dá)量下降，即病毒抑制HS表達(dá)。對(duì)此，郭博士展開(kāi)詳細(xì)研究，他發(fā)現(xiàn)PRRSV在感染晚期，病毒需要從細(xì)胞膜表面釋放出來(lái)，而此時(shí)膜上的HS會(huì)與病毒相互黏連，抑制病毒釋放，即HS受體是一把雙刃劍。PRRSV為了釋放出來(lái)，通過(guò)激活NF-κB信號(hào)通路上調(diào)表達(dá)乙酰肝素酶Heparanase，并通過(guò)激活組織蛋白酶Cathepsin L激活Heparanase，激活的Heparanase遷移到細(xì)胞膜上切割HS，抑制其與病毒粒子黏連，從而促進(jìn)病毒釋放（如下圖所示）。

PRRSV釋放模式圖

本研究首次闡述了PRRSV釋放機(jī)制，對(duì)該病毒防控具有重要指導(dǎo)意義。乙酰肝素酶Heparanase可作為抗PRRSV的重要靶位點(diǎn)。對(duì)此，郭春和博士挖掘到鋅離子載體Pyrithione通過(guò)靶向Heparanase抑制病毒復(fù)制，相關(guān)研究成果已申報(bào)國(guó)家發(fā)明專利，并發(fā)表在中科院一區(qū)Veterinary Microbiology雜志上。

Heparanase upregulation contributes to porcine reproductive and respiratory syndrome 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 for initial attachment to target cells. However, the role of HS in the late phase of PRRSV infection and the mechanism of virus release from host cells remain largely unknown. In this study, we showed that PRRSV infection caused a decrease of HS expression and upregulated heparanase, the only known enzyme capable to degrade HS. We subsequently demonstrated that the NF-κB signaling pathway and cathepsin L protease were involved in regulation of PRRSV infection-induced heparanase. 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 suggest that PRRSV activates NF-κB and cathepsin L to upregulate and process heparanase, then the active heparanase cleave HS, resulting in viral release. Our findings provide new insight into the molecular mechanism of PRRSV egress from host cells, which might help us to further understand PRRSV pathogenesis.

原文鏈接：http://jvi.asm.org/content/early/2017/05/04/JVI.00625-17.long

文章來(lái)源/中國(guó)病毒學(xué)論壇

作者/郭春和