Kawaguchi Atsushi, Hirohama Mikako, Harada Yoshimi, Osari Suguru, Nagata Kyosuke
Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tennodai, Tsukuba, Japan.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai, Tsukuba, Japan.
PLoS Pathog. 2015 Nov 17;11(11):e1005284. doi: 10.1371/journal.ppat.1005284. eCollection 2015.
Influenza virus particles are assembled at the plasma membrane in concert with incorporation of the virus genome, but the details of its spatio-temporal regulation are not understood. Here we showed that influenza virus infection induces the assembly of pericentrosomal endocytic recycling compartment (ERC) through the activation of Rab11a GTPase and cell cycle-independent maturation of centrosome by YB-1, a multifunctional protein that is involved in mitotic division, RNA metabolism and tumorigenesis. YB-1 is recruited to the centrosome in infected cells and is required for anchoring microtubules to the centrosome. We also found that viral infection accumulates cholesterol in ERC and is dependent on YB-1. Depletion of YB-1 shows reduced cholesterol-enriched ERC and prevented budozone formation at the plasma membrane. These results suggest that cholesterol in recycling endosomes, which are emanated from ERC, may trigger the virus assembly concomitantly with the packaging of the virus genome. We propose that the virus genome is transported to the plasma membrane by cholesterol-enriched recycling endosomes through cell cycle-independent activation of the centrosome by YB-1.
流感病毒颗粒在病毒基因组整合的同时于质膜处组装，但其时空调节的细节尚不清楚。在此我们表明，流感病毒感染通过激活Rab11a GTP酶诱导中心体周围内吞循环区室（ERC）的组装，并通过YB-1（一种参与有丝分裂、RNA代谢和肿瘤发生的多功能蛋白）实现中心体不依赖细胞周期的成熟。YB-1被招募到受感染细胞的中心体，是微管锚定到中心体所必需的。我们还发现病毒感染使ERC中胆固醇积累，且依赖于YB-1。YB-1的缺失显示富含胆固醇的ERC减少，并阻止了质膜处芽区的形成。这些结果表明，源自ERC的循环内体中的胆固醇可能在病毒基因组包装的同时触发病毒组装。我们提出，病毒基因组通过富含胆固醇的循环内体，经YB-1对中心体的不依赖细胞周期的激活作用，被转运到质膜。
