Nucleotide change of codon 182 in the surface gene of hepatitis B virus genotype C leading to truncated surface protein is associated with progression of liver diseases

Lee, Seoung Ae; Kim, Ki-Jeong; Kim, Hong; Kim, Bum Joon

doi:10.1016/j.jhep.2011.06.028

Cited by 71 publications

(75 citation statements)

References 26 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The predominance of the W4P/R mutations in South Korean patients might be explained by the distinct molecular epidemiologic trait of genotype C, the only genotype which infects South Korean patients at a higher mutation rate. In actuality, recent papers (6)(7)(8)(9)(10)(11)(12)(13)(14) proving the presence of several unique HBV mutation patterns in South Korean patients support the above hypothesis.…”

Section: Figmentioning

confidence: 64%

“…A primer pair (preS1F and preS1R) for amplification of the HBV pre-S1 gene fragment was designed by using Oligo version 6.5 (Molecular Biology Insights), producing a 224-bp amplicon. An anchor probe and a sensor probe for the identification of mu- (12). A LightCycler 2.0 system was used, and its detection channels were calibrated for color compensation and activated for the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…South Korea is recognized as an area where HBV infection is endemic; based on the Korean National Health and Nutrition Survey of 2007, the prevalence of HBsAg was 4.2% in men and 3.1% in women at that time (4). Moreover, it was reported that the extraordinary prevalence in South Korea of HBV genotype C2, which is known to be more virulent than HBV genotype B (5), might contribute to the distribution of the characteristic HBV mutation patterns related to the progression of liver diseases (6)(7)(8)(9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Male-Specific W4P/R Mutation in the Pre-S1 Region of Hepatitis B Virus, Increasing the Risk of Progression of Liver Diseases in Chronic Patients

Lee

Kim²,

Kim

et al. 2013

J Clin Microbiol

Self Cite

View full text Add to dashboard Cite

bThe issue of hepatitis B virus (HBV) mutations possibly leading to a gender disparity in the progression of liver diseases has not been explored. We aimed to elucidate the relationships of the novel pre-S1 mutations, W4P/R, with the progression of liver diseases and male predominance in a South Korean chronic cohort by use of a molecular epidemiologic study. We developed a fluorescence resonance energy transfer (FRET)-based real-time PCR (RT-PCR) assay for the detection of the W4P/R mutations and applied it to 292 chronic HBV patients. The pre-S1 mutations from 247 (84.6%) of a total of 292 patients were detected by this assay. W4P/R mutants were found to be significantly related to severe liver diseases (hepatocellular carcinoma [HCC] and liver cirrhosis, 12.4% [19/153] of patients, versus chronic hepatitis and asymptomatic carriage, 1.1% [1/94] of patients) (P < 0.001). All of the W4P/R mutants were found in males only. The novel HBV pre-S1 mutations, W4P/R, may be associated with disease severity in male patients chronically infected with HBV genotype C. The W4P/R mutations may provide in part an explanation for the relatively high ratio of male to female incidence in HCC generation in South Korean chronic HBV patients. Hepatitis B virus (HBV) infection is a global health problem, and Ͼ350 million people are chronic carriers of the virus (1, 2). The infection is associated with a wide spectrum of clinical manifestations, ranging from acute or fulminant hepatitis to various forms of chronic infection, including asymptomatic carriage, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) (3). South Korea is recognized as an area where HBV infection is endemic; based on the Korean National Health and Nutrition Survey of 2007, the prevalence of HBsAg was 4.2% in men and 3.1% in women at that time (4). Moreover, it was reported that the extraordinary prevalence in South Korea of HBV genotype C2, which is known to be more virulent than HBV genotype B (5), might contribute to the distribution of the characteristic HBV mutation patterns related to the progression of liver diseases (6-14).HBV produces three envelope proteins, all of which are encoded in the pre-S/S open reading frame. They have been suggested to play a role in virus assembly (15, 16) and attachment to hepatocytes (17). It has also been proposed that large surface proteins (LHBs) with mutations, particularly deletions, in the Pre-S region might contribute to hepatocarcinogenesis through the induction of an endoplasmic reticulum (ER) stress pathway or trans-activating capacity (18-20). HBV pre-S mutations prevail in countries where HBV infection is highly endemic. In general, the Pre-S2 region is known to be more prone to mutations than the Pre-S1 region. Therefore, so far, the mutation patterns related to the progression of liver disease have been described more frequently in the Pre-S2 than in the Pre-S1 region. Recently, we showed a novel pre-S1 deletion type leading to 11 amino acid deletions from the pre-S1 start codon that is related t...

show abstract

Section: Figmentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Male-Specific W4P/R Mutation in the Pre-S1 Region of Hepatitis B Virus, Increasing the Risk of Progression of Liver Diseases in Chronic Patients

Lee

Kim²,

Kim

et al. 2013

J Clin Microbiol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Acute infection with genotypes A and D leads to higher rate of chronicity than genotypes B and C (28)(29)(30). Genotype C generally is considered as a risk factor for perinatal infection (31) and related to severe liver disease, including cirrhosis and HCC (32)(33)(34). In the interferon therapy, patients with genotypes A and B have better treatment response than genotypes C and D (35).…”

Section: Hbv Genotypingmentioning

confidence: 99%

Diagnosis of hepatitis B

Song

Kim

2016

Ann. Transl. Med.

View full text Add to dashboard Cite

Hepatitis B virus (HBV) infection is a major global health problems leading to severe liver disease such as cirrhosis and hepatocellular carcinoma (HCC). HBV is a circular, partly double-stranded DNA virus with various serological markers: hepatitis B surface antigen (HBsAg) and anti-HBs, anti-HBc IgM and IgG, and hepatitis B e antigen (HBeAg) and anti-HBe. It is transmitted by sexual, parenteral and vertical route. One significant method to diminish the burden of this disease is timely diagnosis of acute, chronic and occult cases of HBV. First step of HBV diagnosis is achieved by using serological markers for detecting antigens and antibodies. In order to verify first step of diagnosis, to quantify viral load and to identify genotypes, quantitative or qualitative molecular tests are used. In this article, the serological and molecular tests for diagnosis of HBV infection will be reviewed.

show abstract

“…Moreover, an extraordinary prevalence of genotype C2 was reported in this area [3] . This genotype is more virulent than genotype B [4] , and it may contribute to the distribution of characteristic HBV mutation patterns that are related to the progression of liver diseases [5][6][7][8][9][10][11][12][13][14][15] . HBV surface open reading frames (ORFs) encode 3 types of proteins that share C terminals, large (L), middle (M), and small (S) surface antigen.…”

Section: Introductionmentioning

confidence: 99%

Induction of endoplasmic reticulum-derived oxidative stress by an occult infection related S surface antigen variant

Lee¹,

Lee²,

Kim³

et al. 2015

WJG

Self Cite

View full text Add to dashboard Cite

AIM:To investigate the mechanism of endoplasmic reticulum (ER) stress induction by an occult infection related hepatitis B virus S surface antigen (HBsAg) variant. METHODS:We used an HBsAg variant with lower secretion capacity, which was a KD variant from a Korean subject who was occultly infected with the genotype C. We compared the expression profiles of ER stress-related proteins between HuH-7 cells transfected with HBsAg plasmids of a wild-type and a KD variant using Western blot. RESULTS:Confocal microscopy indicated that the KD variant had higher levels of co-localization with ER than the wild-type HBsAg. The KD variant upregulated ER stress-related proteins and induced reactive oxygen species (ROS) compared to the wildtype via an increase in calcium. The KD variant also down-regulated anti-oxidant proteins (HO-1, catalase and SOD) compared to the wild-type, which indicates positive amplification loops of the ER-ROS axis. The KD variant also induced apoptotic cell death via the upregulation of caspase proteins (caspase 6, 9 and 12). Furthermore, the KD variant induced a higher level of nitric oxide than wild-type HBsAg via the up-regulation of the iNOS protein. CONCLUSION:Our data indicate that occult infection related HBsAg variants can lead to ER-derived oxidative stress and liver cell death in HuH-7 cells.

show abstract

Nucleotide change of codon 182 in the surface gene of hepatitis B virus genotype C leading to truncated surface protein is associated with progression of liver diseases

Cited by 71 publications

References 26 publications

Male-Specific W4P/R Mutation in the Pre-S1 Region of Hepatitis B Virus, Increasing the Risk of Progression of Liver Diseases in Chronic Patients

Male-Specific W4P/R Mutation in the Pre-S1 Region of Hepatitis B Virus, Increasing the Risk of Progression of Liver Diseases in Chronic Patients

Diagnosis of hepatitis B

Induction of endoplasmic reticulum-derived oxidative stress by an occult infection related S surface antigen variant

Contact Info

Product

Resources

About