Files and links (1)
Accepted (AM)Open Access (License Unspecified), Open
Journal article
CpAMs induce assembly of HBV capsids with altered electrophoresis mobility: Implications for mechanism of inhibiting pgRNA packaging
Antiviral research, v 159, pp 1-12
01 Nov 2018
PMID: 30201396
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Native agarose gel electrophoresis-based particle gel assay has been commonly used for examination of hepatitis B virus (HBV) capsid assembly and pregenomic RNA encapsidation in HBV replicating cells. Interestingly, treatment of cells with several chemotypes of HBV core protein allosteric modulators (CpAMs) induced the assembly of both empty and DNA-containing capsids with faster electrophoresis mobility. In an effort to determine the physical basis of CpAM-induced capsid mobility shift, we found that the surface charge, but not the size, of capsids is the primary determinant of electrophoresis mobility. Specifically, through alanine scanning mutagenesis analysis of twenty-seven charged amino acids in core protein assembly domain and hinge region, we showed that except for K7 and E8, substitution of glutamine acid (E) or aspartic acid (D) on the surface of capsids reduced their mobility, but substitution of lysine (K) or arginine (R) on the surface of capsids increased their mobility in variable degrees. However, alanine substitution of the charged amino acids that are not exposed on the surface of capsid did not apparently alter capsid mobility. Hence, CpAM-induced electrophoresis mobility shift of capsids may reflect the global alteration of capsid structure that changes the exposure and/or ionization of charged amino acid side chains of core protein. Our findings imply that CpAM inhibition of pgRNA encapsidation is possibly due to the assembly of structurally altered nucleocapsids. Practically, capsid electrophoresis mobility shift is a diagnostic marker of compounds that target core protein assembly and predicts sensitivity of HBV strains to specific CpAMs.
Metrics
Details
- Title
- CpAMs induce assembly of HBV capsids with altered electrophoresis mobility: Implications for mechanism of inhibiting pgRNA packaging
- Creators
- Shuo Wu - Baruch S. Blumberg InstituteYue Luo - Second Xiangya Hospital of Central South UniversityUsha Viswanathan - Baruch S. Blumberg InstituteJohn Kulp - Baruch S. Blumberg InstituteJunjun Cheng - Baruch S. Blumberg InstituteZhanying Hu - Baruch S. Blumberg InstituteQifang Xu - Fox Chase Cancer CenterYan Zhou - Fox Chase Cancer CenterGuo-Zhong Gong - Cent S Univ, Inst Hepatol, Xiangya Hosp 2, Changsha, Hunan, Peoples R ChinaJinhong Chang - Baruch S. Blumberg InstituteYuhuan Li - College Station Medical CenterJu-Tao Guo - Baruch S. Blumberg Institute
- Publication Details
- Antiviral research, v 159, pp 1-12
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- 2017350008 / Peking Union Medical College Youth Fund AI113267 / National Institutes of Health, USA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000449132700001
- Scopus ID
- 2-s2.0-85053141661
- Other Identifier
- 991020547606004721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy
- Virology