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Journal article
Hepatitis B virus nucleocapsid uncoating: biological consequences and regulation by cellular nucleases
Emerging microbes & infections, v 10(1), pp 852-864
01 Jan 2021
PMID: 33870849
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Upon infection of hepatocyte, Hepatitis B virus (HBV) genomic DNA in nucleocapsid is transported into the nucleus and converted into a covalently closed circular (ccc) DNA to serve as the template for transcription of viral RNAs. Viral DNA in the cytoplasmic progeny nucleocapsid is another resource to fuel cccDNA amplification. Apparently, nucleocapsid disassembly, or viral genomic DNA uncoating, is an essential step for cccDNA synthesis from both de novo infection and intracellular amplification pathways, and has a potential to activate DNA sensors and induce an innate immune response in infected hepatocytes. However, where and how the nucleocapsid disassembly occurs is not well understood. The work reported herein showed that the enhanced disassembly of progeny mature nucleocapsids in the cytoplasm supported cccDNA intracellular amplification, but failed to activate the cGAS-STING-mediated innate immune response in hepatocytes. Interestingly, while expression of a cytoplasmic exonuclease TREX1 in human hepatoma cells supporting HBV replication significantly reduced the amounts of cccDNA as well as its precursor, deproteinized relaxed circular (rc) DNA, expression of TREX1 in sodium taurocholate cotransporting polypeptide-expressing human hepatoma cells did not inhibit cccDNA synthesis from de novo HBV infection. The results from this cytoplasmic nuclease protection assay imply that the disassembly of progeny mature nucleocapsids and removal of viral DNA polymerase covalently linked to the 5′ end of minus strand of rcDNA take place in the cytoplasm. On the contrary, the disassembly of virion-derived nucleocapsids during de novo infection may occur at a different subcellular compartment and possibly via distinct mechanisms.
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Details
- Title
- Hepatitis B virus nucleocapsid uncoating: biological consequences and regulation by cellular nucleases
- Creators
- Jin Hu - Chinese Academy of Medical Sciences & Peking Union Medical CollegeLiudi Tang - Drexel UniversityJunjun Cheng - Baruch S. Blumberg InstituteTianlun Zhou - Baruch S. Blumberg InstituteYuhuan Li - Chinese Academy of Medical Sciences and Peking Union Medical CollegeJinhong Chang - Baruch S. Blumberg InstituteQiong Zhao - Baruch S. Blumberg InstituteJu-Tao Guo - Baruch S. Blumberg Institute
- Publication Details
- Emerging microbes & infections, v 10(1), pp 852-864
- Publisher
- Taylor & Francis
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000646038000001
- Scopus ID
- 2-s2.0-85105767713
- Other Identifier
- 991019168258404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases
- Microbiology