J Virol:中国农业科学院王晓钧研究组揭示动物慢病毒Gag蛋白细胞
近日，国际著名病毒学专业期刊《Journal of Virology》上在线发表中国农业科学院哈尔滨兽医研究所王晓钧研究员领衔的马传染病和慢病毒病研究团队题为Equine Infectious Anemia virus Gag Assembly and Export Are Directed by Matrix Protein through trans-Golgi Networks and Cellular Vesicles《基质蛋白介导马传染性贫血病毒经由高尔基网络和囊泡的组装和释放》的一篇文章，研究报道EIAV病毒Gag蛋白细胞内组装和释放机制。张泽力和马建作为文章共同第一作者，王晓钧研究员为论文通讯作者。
反转录病毒科慢病毒属成员众多，包括人获得性免疫缺陷病毒(HIV-1)和马传染性贫血病毒(EIAV)等，可感染人和多种动物并引发严重疾病。在慢病毒病原学与致病机制研究领域，开展结构蛋白Gag在细胞内的组装及向胞外释放机制研究，是明确病毒生活史、与宿主细胞间相互作用、及寻找预防、治疗慢病毒感染方法的有效手段。
王晓钧研究员率领其研究团队，关注该研究热点，从比较病毒学角度，开展了EIAV与HIV-1二者Gag蛋白细胞内的组装与释放机制的比较研究。研究发现，与HIV-1 Gag主要定位于细胞膜内缘不同，EIAV Gag显示出明显的定位于细胞内膜的特性，而基质蛋白MA决定 EIAV Gag的细胞内定位和释放，其氨基端9个氨基酸基序发挥关键作用。此外，研究发现高尔基体外侧网络结构(TGN)很有可能是EIAV Gag所利用的细胞内组装场所，且细胞内的分泌泡参与EIAV病毒粒子的释放，但内体/多泡体并不是EIAV Gag细胞内定位和释放所利用主要内膜结构。
研究数据提示了不同慢病毒与宿主细胞间作用特征的多样性。该研究成果有助于全面认识慢病毒属成员的病毒生物学特征，可促进有效慢病毒防治策略的探索。
原文链接：
Equine Infectious Anemia Virus Gag Assembly and Export Are Directed by Matrix Protein through trans-Golgi Networks and Cellular Vesicles
原文摘要：
Gag intracellular assembly and export are very important processes for lentiviruses replication. Previous studies have demonstrated that equine infectious anemia virus (EIAV) MA possesses distinct phosphoinositide affinity compared with HIV-1 MA and that phosphoinositide-mediated targeting to peripheral and internal membranes is a critical factor in EIAV assembly and release. In this study, we compared the cellular assembly sites of EIAV and HIV-1. We observed that the assembly of EIAV particles occurred on interior cellular membranes, while HIV-1 was targeted to the PM for assembly. Then, we determined that W7 and K9 in the EIAV MA N-terminus were essential for Gag assembly and release but did not affect the cellular distribution of Gag. The replacement of EIAV MA with HIV-1 MA directed chimeric Gag to the PM but severely impaired Gag release. MA structural analysis indicated that the EIAV and HIV-1 MAs had similar spatial structures but that helix 1 of the EIAV MA was closer to loop 2. Further investigation indicated that EIAV Gag accumulated in the trans-Golgi network (TGN) but not the early and late endosomes. The 9 N-terminal amino acids of EIAV MA harbored the signal that directed Gag to the TGN membrane system. Additionally, we demonstrated that EIAV particles were transported to the extracellular space by the cellular vesicle system. This type of EIAV export was not associated with multivesicular bodies (MVBs) or microtubule depolymerization but could be inhibited by the actin-depolymerizing drug cytochalasin D, suggesting that dynamic actin depolymerization may be associated with EIAV production.
作者：王晓钧
