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Viruses 2017, 9(4), 62; doi:10.3390/v9040062

The Envelope Gene of Hepatitis B Virus Is Implicated in Both Differential Virion Secretion and Genome Replication Capacities between Genotype B and Genotype C Isolates

1
Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
2
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200032, China
3
Liver Research Center, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI 02903, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Joanna Parish
Received: 20 December 2016 / Revised: 7 March 2017 / Accepted: 20 March 2017 / Published: 28 March 2017
(This article belongs to the Section Animal Viruses)
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Abstract

Chronic infection by hepatitis B virus (HBV) genotype C is associated with a prolonged replicative phase and an increased risk of liver cancer, compared with genotype B infection. We previously found lower replication capacity but more efficient virion secretion by genotype C than genotype B isolates. Virion secretion requires interaction between core particles and ENVELOPE proteins. In the present study, chimeric constructs between genotype B and genotype C clones were generated to identify the structural basis for differential virion secretion. In addition to dimeric constructs, we also employed 1.1mer constructs, where the cytomegalovirus (CMV) promoter drove pregenomic RNA transcription. Through transient transfection experiments in Huh7 cells, we found that exchanging the entire envelope gene or just its S region could enhance virion secretion by genotype B clones while diminishing virion secretion by genotype C. Site-directed mutagenesis established the contribution of genotype-specific divergence at codons 108 and 115 in the preS1 region, as well as codon 126 in the S region, to differential virion secretion. Surprisingly, exchanging the envelope gene or just its S region, but not the core gene or 3′ S region, could markedly increase intracellular replicative DNA for genotype C clones but diminish that for genotype B, although the underlying mechanism remains to be clarified. View Full-Text
Keywords: core gene; envelope gene; genome replication; genotype; hepatitis B virus; virion secretion core gene; envelope gene; genome replication; genotype; hepatitis B virus; virion secretion
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Jia, H.; Qin, Y.; Chen, C.; Zhang, F.; Li, C.; Zong, L.; Wang, Y.; Zhang, J.; Li, J.; Wen, Y.; Tong, S. The Envelope Gene of Hepatitis B Virus Is Implicated in Both Differential Virion Secretion and Genome Replication Capacities between Genotype B and Genotype C Isolates. Viruses 2017, 9, 62.

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