title: 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.
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 entireenvelopegene or just itsSregion 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 thepreS1region, as well as codon 126 in theSregion, to differential virion secretion. Surprisingly, exchanging theenvelopegene or just itsSregion, but not thecoregene or 3'Sregion, could markedly increase intracellular replicative DNA for genotype C clones but diminish that for genotype B, although the underlying mechanism remains to be clarified.
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. hdjia14@fudan.edu.cn.
authors.forename: Haodi
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200032, China. qyl2122@hotmail.com.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 13111010065@fudan.edu.cn.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 13817459252@126.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 15211010047@fudan.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. zongli1226@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zong
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. boldawing@aliyun.com.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200032, China. jmzhang@fudan.edu.cn.
authors.forename: Jiming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Liver Research Center, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI 02903, USA. ji_su_li_md@brown.edu.
authors.forename: Jisu
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. ymwen@shmu.edu.cn.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. shuping_tong_md@brown.edu.|Liver Research Center, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, Providence, RI 02903, USA. shuping_tong_md@brown.edu.
authors.forename: Shuping
authors.initials: S
authors.lastname: Tong
mesh_terms: D002460:Cell Line; D004252:DNA Mutational Analysis; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D016297:Mutagenesis, Site-Directed; D011995:Recombination, Genetic; D014759:Viral Envelope Proteins / Q000378:metabolism*; D057074:Virus Release; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins
keywords: core gene; envelope gene; genome replication; genotype; hepatitis B virus; virion secretion