EB 病毒 BGLF4 透過調控細胞骨架以協助病毒細胞質組裝區域之形成

Abstract

Epstein-Barr virus (EBV) is the first human virus to be implicated in carcinogenesis. Over 90 percent of people are infected by EBV in the world. Upon lytic replication, the nucleocapsids of EBV need to be translocated from the nucleus into cytoplasm for tegumentation and final maturation after DNA replication and encapsidation. Little is known about how EBV remodels cytoskeleton and cellular secretory apparatuses for efficient cytoplasmic assembly. Using EBV infected nasopharyngeal carcinoma NA cells we showed that, cells displayed modified nuclear structure after EBV reactivation. Viral capsid, tegument proteins and glycoproteins are clustered at juxtanuclear concave region accompanied by redistributed cytoplasmic organelles, MTOC and cytoskeleton regulator IQGAP1, suggesting EBV builds a specialized cytoplasmic assembly compartment for an efficient cytoplasmic maturation process. This compartment was disrupted after siRNA knockdown of BGLF4 kinase. Transient expression of BGLF4 induced a compact Golgi structure along with reorganization of MTOC and IQGAP1, indicating that BGLF4 plays a critical role for assembly compartment formation and cytoskeleton rearrangement. Treatment with microtubule-disturbing agents in cells inhibited BGLF4 induced compact Golgi structure, suggesting BGLF4 induces assembly compartment formation through regulation of cytoskeleton rearrangement. Since BGLF4 interacted with IQGAP1 in co-immunoprecipitation assay and phosphorylated IQGAP1 in vitro,it is possible that BGLF4 regulates cytoskeleton through phosphorylation of IQGAP1. While viral DNA replication and maturation was enhanced in IQGAP1 knockdown cells, IQGAP1 may serve as a negative regulator of EBV lytic cycle. Taken together, I propose that BGLF4 induces cytoskeleton rearrangement and instability through phosphorylation of IQGAP1, and subsequently facilitates assembly compartment formation and virus maturation.