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Core promoter mutation of nucleotides A1762T and G1764A of hepatitis B virus increases core promoter transactivation by hepatocyte nuclear factor 1
Mi So Seong , Hyeon Jeong Hwang , Eun Ah Jang , Jeong Ah Jang , Wah Wah Aung , Yi Yi Kyaw , JaeHun Cheong
J. Microbiol. 2022;60(10):1039-1047.   Published online September 27, 2022
DOI: https://doi.org/10.1007/s12275-022-1675-1
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AbstractAbstract
Hepatitis B virus (HBV) infection highly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). The clinical manifestation of HBV infection is determined by the mutual interplay of the viral genotype, host genetic factors, mode of transmission, adaptive mutations, and environmental factors. Core promoter activation plays a critical role in the pre-genomic RNA transcription of HBV for HBV replication. The mutations of core promoter have been implicated in HCC development. We had obtained HBV genes from Myanmar HBV infectants and identified gene variations at the core promoter region. For measuring the relative transactivation activity on core promoter, we prepared the core-promoter reporter construct. Both of A1762T and G1764A mutation were consistently found in the HBV genes with hepatocellular carcinoma. The A1762T/G1764A mutation was corresponding to K130M/V131I of HBx protein. We prepared the core promoter- luciferase reporter construct containing the double A1762T/G1764A mutation and the K130M/V131I HBx protein expression construct. The A1762T/G1764A mutation highly was responsive to core promoter transactivation by HBx, regardless of HBx mutation. The A1762T/G1764A mutation newly created hepatocyte nuclear factor 1 (HNF1) responsive element. Ectopic expression of HNF1 largely increased the HBV core promoter containing A1762T/G1764A mutation. In addition, hepatic rich fatty acid, palmitic acid and oleic acid, increased K130M/V131I HBx level by core promoter activation. These results provide biological properties and clinical significance of specific HBV core promoter mutants related with HCC development.

Citations

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  • A Survey of HBV Core/Pre-Core Mutations in Iraqi Patients with Chronic Hepatitis
    Abdulhussain Kadhim Jwaziri, Maryam Esghaei, Mohammad Hadi Karbalaie Niya, Hadi Sayah, Mohammad Hossein Razizadeh, Ali Gholami, Leila Mousavizadeh, Hossein Keyvani
    Hepatitis Monthly.2023;[Epub]     CrossRef
  • The A1762T/G1764A mutations enhance HBV replication by alternating viral transcriptome
    Danli Yang, Jun Zou, Guiwen Guan, Xiaoyu Feng, Ting Zhang, Guixin Li, Hui Liu, Huiling Zheng, Jingyuan Xi, Guangxin Yu, Lizhong Dai, Fengmin Lu, Xiangmei Chen
    Journal of Medical Virology.2023;[Epub]     CrossRef
  • Clinical application value of hepatitis B virus basal core promoter 1762/1764 and GGTII and GGT in patients with HBV-DNA-positive primary liver cancer
    Shunhua Qiu, Lifen Jin, Dan Yang, Dewen Zhang
    Medicine.2023; 102(43): e35699.     CrossRef

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