Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional Cure

Autor: Masaaki Shiina, Masatoshi Ishigami, Takanori Ito, Teiji Kuzuya, Asuka Kato, Norie Yamada, Takanobu Kato, Tetsuya Ishikawa, Masamichi Muramatsu, Mitsuhiro Fujishiro, Tomohisa Tanaka, Kohji Moriishi, Yoji Ishizu, Yoshiki Murakami, Hussein H. Aly, Hironori Nishitsuji, Kunitada Shimotohno, Asako Murayama, Takaji Wakita, Takashi Honda
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
GEq
genome equivalent
HBVcc
cell culture-generated HBV
Clone (cell biology)
Cell Culture Techniques
RC799-869
medicine.disease_cause
Virus Replication
SS
single-stranded HBV DNA
NL
NanoLuc luciferase
PCR
polymerase chain reaction
Genes
Reporter
Original Research
Infectivity
RT
reverse transcription
HBc
Gastroenterology
virus diseases
RLU
relative light units
cccDNA
Transfection
Hepatitis B
Diseases of the digestive system. Gastroenterology
Middle Aged
HBsAg
hepatitis B surface antigen
Disease Progression
CHB
chronic hepatitis B
Female
cccDNA
covalently closed circular DNA
Genetic Engineering
wt
wild-type
Adult
Gene Expression Regulation
Viral
Hepatitis B virus
SDS
sodium dodecyl sulfate
HBeAg
hepatitis B e antigen
Biology
Models
Biological
Virus
RC
relaxed-circular HBV DNA
Viral Proteins
Hepatitis B
Chronic
HBcrAg
hepatitis B core-related antigen
ALT
alanine aminotransferase
medicine
HBVcc
Humans
IFN
interferon
Hepatitis
Polymorphism
Genetic
Hepatology
pgRNA
pregenomic RNA
HBc
hepatitis B core
NA
nucleos(t)ide analog
medicine.disease
Virology
digestive system diseases
HBV
hepatitis B virus
Amino Acid Substitution
DNA
Viral
SD
standard deviation
Biomarkers
DAPI
4′
6-diamidino-2-phenylindole
Zdroj: Cellular and Molecular Gastroenterology and Hepatology
Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 5, Pp 1583-1598 (2021)
ISSN: 2352-345X
Popis: Background & Aims To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine at amino acid 97 (I97L) in the hepatitis B core region as a key predictor among patients with stable hepatitis. In this study, we attempted to identify the point at which I97L affects the hepatitis B virus (HBV) life cycle and to elucidate the underlying mechanisms governing the stabilization of hepatitis. Methods To confirm the clinical features of I97L, we used a cohort of hepatitis B e antigen–negative patients with chronic hepatitis B infected with HBV-I97 wild-type (wt) or HBV-I97L. The effects of I97L on viral characteristics were evaluated by in vitro HBV production and infection systems with the HBV reporter virus and cell culture-generated HBV. Results The ratios of reduction in hepatitis B surface antigen and HBV DNA were higher in patients with HBV-I97L than in those with HBV-I97wt. HBV-I97L exhibited lower infectivity than HBV-I97wt in both infection systems with reporter HBV and cell culture-generated HBV. HBV-I97L virions exhibiting low infectivity primarily contained a single-stranded HBV genome. The lower efficiency of cccDNA synthesis was demonstrated after infection of HBV-I97L or transfection of the molecular clone of HBV-I97L. Conclusions The I97L substitution reduces the level of cccDNA through the generation of immature virions with single-stranded genomes. This I97L-associated low efficiency of cccDNA synthesis may be involved in the stabilization of hepatitis.
Graphical abstract
Databáze: OpenAIRE
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