CRM1-spike-mediated nuclear export of hepatitis B virus encapsidated viral RNA

被引：20

作者：

Yang, Ching-Chun ^{[1
,2
,3
]}

Chang, Chih-Hsu ^{[3
,4
,5
]}

Chen, Heng-Li ^{[3
]}

Chou, Ming-Chieh ^{[3
,4
]}

Yang, Ching-Jen ^{[3
]}

Jhou, Ren-Shiang ^{[3
]}

Huang, Er-Yi ^{[3
]}

Li, Hung-Cheng ^{[3
]}

Suen, Ching-Shu ^{[3
]}

Hwang, Ming-Jing ^{[3
]}

Shih, Chiaho ^{[3
,4
]}

机构：

[1] Natl Yang Ming Univ, Taiwan Int Grad Program TIGP Mol Med, Taipei 112, Taiwan

[2] Acad Sinica, Taipei 112, Taiwan

[3] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan

[4] Kaohsiung Med Univ, Grad Inst Med, Kaohsiung 807, Taiwan

[5] Natl Taiwan Univ, Coll Med, Grad Inst Microbiol, Taipei 100, Taiwan

来源：

CELL REPORTS | 2022年 / 38卷 / 10期

关键词：

ARGININE-RICH DOMAIN; CORE-ANTIGEN; PORE COMPLEX; HEPATOCYTE NUCLEAR; CRYSTAL-STRUCTURE; REPLICATION; PARTICLES; PROTEIN; LOCALIZATION; TRANSPORT;

D O I：

10.1016/j.celrep.2022.110472

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Hepatitis B virus (HBV) is a global pathogen. We report here that the cellular CRM1 machinery can mediate nuclear export of entire HBV core (HBc) particles containing encapsidated viral RNAs. Two CRM1-mediated nuclear export signals (NESCRM1) cluster at the conformationally flexible spike tips of HBc particles. Mutant NESCRM1 capsids exhibit strongly reduced associations with CRM1 and nucleoporin358 in vivo. CRM1 and NXF1 machineries mediate nuclear export of HBc particles independently. Inhibition of nuclear export has pleiotropic consequences, including nuclear accumulation of HBc particles, a significant reduction of encapsidated viral RNAs in the cytoplasm but not in the nucleus, and barely detectable viral DNA. We hypothesize an HBV life cycle where encapsidation of the RNA pregenome can initiate early in the nucleus, whereas DNA genome maturation occurs mainly in the cytoplasm. We identified a druggable target for HBV by blocking its intracellular trafficking.

引用

页数：20

共 65 条

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