scholarly journals Additional N-glycosylation mutation in the major hydrophilic region of hepatitis B virus S gene is a risk indicator for hepatocellular carcinoma occurrence in patients with coexistence of HBsAg/anti-HBs

Oncotarget ◽  
2017 ◽  
Vol 8 (37) ◽  
pp. 61719-61730 ◽  
Author(s):  
Yan Qiao ◽  
Shanshan Lu ◽  
Zhihui Xu ◽  
Xiaodong Li ◽  
Kai Zhang ◽  
...  
2017 ◽  
Vol 162 (10) ◽  
pp. 2949-2957 ◽  
Author(s):  
Siping Li ◽  
Mingyu Xie ◽  
Wenrui Li ◽  
Qi Peng ◽  
Baimao Zhong ◽  
...  

2014 ◽  
Vol 60 (3) ◽  
pp. 515-522 ◽  
Author(s):  
De-Min Yu ◽  
Xin-Hua Li ◽  
Vannary Mom ◽  
Zhong-Hua Lu ◽  
Xiang-Wei Liao ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 862
Author(s):  
Yueh-Te Lin ◽  
Long-Bin Jeng ◽  
Wen-Ling Chan ◽  
Ih-Jen Su ◽  
Chiao-Fang Teng

Hepatocellular carcinoma (HCC) is one of the most frequent and fatal human cancers worldwide and its development and prognosis are intimately associated with chronic infection with hepatitis B virus (HBV). The identification of genetic mutations and molecular mechanisms that mediate HBV-induced tumorigenesis therefore holds promise for the development of potential biomarkers and targets for HCC prevention and therapy. The presence of HBV pre-S gene deletions in the blood and the expression of pre-S deleted proteins in the liver tissues of patients with chronic hepatitis B and HBV-related HCC have emerged as valuable biomarkers for higher incidence rates of HCC development and a higher risk of HCC recurrence after curative surgical resection, respectively. Moreover, pre-S deleted proteins are regarded as important oncoproteins that activate multiple signaling pathways to induce DNA damage and promote growth and proliferation in hepatocytes, leading to HCC development. The signaling molecules dysregulated by pre-S deleted proteins have also been validated as potential targets for the prevention of HCC development. In this review, we summarize the clinical and molecular implications of HBV pre-S gene deletions and pre-S deleted proteins in HCC development and recurrence and highlight their potential applications in HCC prevention and therapy.


2015 ◽  
Vol 143 (16) ◽  
pp. 3572-3582 ◽  
Author(s):  
X. Y. WANG ◽  
T. J. HARRISON ◽  
X. HE ◽  
Q. Y. CHEN ◽  
G. J. LI ◽  
...  

SUMMARYMutations in the major hydrophilic region (MHR) of the surface antigen of hepatitis B virus (HBV) may result in vaccine escape, failure of immunotherapy and antiviral resistance. These mutants may be transmitted and constitute a public health threat. We aimed to determine the prevalence of MHR mutations of HBV in areas of high endemicity in Guangxi, China. HBV surface gene was analysed from 278 HBsAg-positive asymptomatic individuals recruited from Guangxi using cluster sampling. Three genotypes, B, C and I, were identified. The overall prevalence of MHR mutations is 17·6%. The prevalence of MHR mutations in genotype B (15·1%) is not significantly different from that in genotype C (16·4%). However, the prevalence in subgenotype C5 (31·1%) is significantly higher than in subgenotype C2 (13·0%) (χ2= 6·997,P< 0·05). The prevalence of escape mutations and overlapping polymerase substitutions in subgenotype C5 is significantly higher than in subgenotypes B2 and C2. In total, 7·9% of MHR mutants are escape mutations and 72·1% of MHR mutations produced amino-acid changes in the overlapping polymerase, including resistance mutations to entecavir. Our results suggest that the prevalence of MHR mutations varies with subgenotype. The prevalence of escape mutations and polymerase mutations may be associated with subgenotype.


2015 ◽  
Vol 53 (10) ◽  
pp. 3165-3175 ◽  
Author(s):  
Laura Navika Yamani ◽  
Yoshihiko Yano ◽  
Takako Utsumi ◽  
Juniastuti ◽  
Hadi Wandono ◽  
...  

Quasispecies of hepatitis B virus (HBV) with variations in the major hydrophilic region (MHR) of the HBV surface antigen (HBsAg) can evolve during infection, allowing HBV to evade neutralizing antibodies. These escape variants may contribute to chronic infections. In this study, we looked for MHR variants in HBV quasispecies using ultradeep sequencing and evaluated the relationship between these variants and clinical manifestations in infected patients. We enrolled 30 Indonesian patients with hepatitis B infection (11 with chronic hepatitis and 19 with advanced liver disease). The most common subgenotype/subtype of HBV was B3/adw (97%). The HBsAg titer was lower in patients with advanced liver disease than that in patients with chronic hepatitis. The MHR variants were grouped based on the percentage of the viral population affected: major, ≥20% of the total population; intermediate, 5% to <20%; and minor, 1% to <5%. The rates of MHR variation that were present in the major and intermediate viral population were significantly greater in patients with advanced liver disease than those in chronic patients. The most frequent MHR variants related to immune evasion in the major and intermediate populations were P120Q/T, T123A, P127T, Q129H/R, M133L/T, and G145R. The major population of MHR variants causing impaired of HBsAg secretion (e.g., G119R, Q129R, T140I, and G145R) was detected only in advanced liver disease patients. This is the first study to use ultradeep sequencing for the detection of MHR variants of HBV quasispecies in Indonesian patients. We found that a greater number of MHR variations was related to disease severity and reduced likelihood of HBsAg titer.


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