CRM1-spike-mediated nuclear export of hepatitis B virus encapsidated viral RNA
Ching-Chun Yang,
Chih-Hsu Chang,
Heng-Li Chen,
Ming-Chieh Chou,
Ching-Jen Yang,
Ren-Shiang Jhou,
Er-Yi Huang,
Hung-Cheng Li,
Ching-Shu Suen,
Ming-Jing Hwang,
Chiaho Shih
Affiliations
Ching-Chun Yang
Taiwan International Graduate Program (TIGP) in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 112, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
Chih-Hsu Chang
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
Heng-Li Chen
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
Ming-Chieh Chou
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Ching-Jen Yang
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
Ren-Shiang Jhou
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
Er-Yi Huang
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
Hung-Cheng Li
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
Ching-Shu Suen
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
Ming-Jing Hwang
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
Chiaho Shih
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Corresponding author
Summary: 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.
