甲病毒单轮感染颗粒的构建及其应用

Construction and application of single-round infectious particles of alphaviruses

甲病毒(alphavirus)主要包括致关节炎的旧世界甲病毒和引发致命性脑炎的新世界甲病毒,感染人体后可引起严重疾病。为了使用安全方便的工具来研究甲病毒的入侵机制,本研究建立了基于鼠白血病病毒(murine leukemia virus,MLV)的假病毒颗粒和基于新德毕斯病毒(Sindbis virus,SINV)的病毒复制子颗粒(virus replicon particle,VRP)系统。利用包装的假病毒和复制子颗粒,验证了硫酸乙酰肝素生成相关基因B3gat3(beta-1,3-glucuronyltransferase 3)和致关节炎甲病毒入胞受体基因Mxra8(matrix remodeling associated 8)的敲除对不同甲病毒成员入胞的影响。本研究构建的MLV假病毒和SINV复制子颗粒系统,为甲病毒成员的入侵感染机制研究和抗病毒策略开发等提供了安全可靠的实验工具。

Alphaviruses mainly include old-world alphaviruses that cause arthritis and new-world alphaviruses that cause fatal encephalitis,which can lead to serious diseases in humans.In order to establish a safe and convenient tool to study the entry mechanism of alphaviruses,this study established pseudovirus particle system based on murine leukemia virus(MLV)and virus replicon particle(VRP)system based on Sindbis virus(SINV).Using these pseudoviruses and VRPs,the effects of knockout of heparan sulfate biosynthesis-related gene B3gat3(beta-1,3-glucuronyltransferase 3)and arthritogenic alphavirus-related entry receptor gene Mxra8(matrix remodeling associated 8)on cell entry of different alphavirus members were verified.Therefore,the MLV-based pseudoviruses and SINV-based VRP systems in this study provide a safe and reliable experimental tool for the research on the entry mechanism of alphavirus members and the development of antiviral strategy.