Original Article

The mutations frequency of enhancer II/HBx regions of hepatitis B virus in acutely infected Iranian patients: a cross-sectional study

Abstract

Background and Objectives: The viral transactivator HBx protein affect cellular, viral and pregenomic factors pathway. Mutations in this protein can produce new viruses with new antigenic determinants that are generally related to developing cancerous.
Materials and Methods: In this cross-sectional study, 33 serum samples of patients diagnosed with acute HBV infection were investigated for HBeAg and HBV DNA viral load and HBx gene mutations. mutation in the HBx protein detected by sequencing analysis.
Results: Out of the 33 samples, 19 samples were males (57.6%), and 14 samples were females. 15 (45.5%) were positive for HBx DNA and 18 patients were negative for HBx DNA (54.5%). After sequencing, three mutations were recognized in HBx at nucleotide positions 147, 148, and 391 that were stationed to G1524A, G1525A, and G1767C mutations.
Conclusion: The analysis result of this study shows G1524A and G1525A mutations that an important role in altering the inhibition function of the HBx activity domain. The G1767C mutation inactivates HBx transactivation activity. These mutations have a critical role in the pathogenicity of the virus, and the intensity of hepatic tissue demolition and the development of cirrhosis or carcinoma in patients can be understood.

1. Afshar RM, Mollaie HR. Detection of HBV resistance to lamivudine in patients with chronic hepatitis B using Zip nucleic acid probes in Kerman, southeast of Iran. Asian Pac J Cancer Prev 2012; 13: 3657-3661.
2. Slagle BL, Andrisani OM, Bouchard MJ, Lee CGL, Ou JHJ, Siddiqui A. Technical standards for hepatitis B virus X protein (HBx) research. Hepatology 2015; 61: 1416-1424.
3. Neuveut C, Wei Y, Buendia MA. Mechanisms of HBV-related hepatocarcinogenesis. J Hepatol 2010; 52: 594-604.
4. Buonomo AR, Viceconte G, Scotto R, De Angelis M, Tozza S, Manganelli F, et al. Seronegative occult HBV reactivation complicated with fulminant acute liver failure after rituximab for chronic inflammatory demyelinating polyneuropathy. Infect Dis (Lond) 2020; 52: 216-218.
5. Chen S, Wu L, Peng L, Wang X, Tang N. Hepatitis B virus X protein (HBx) promotes ST2 expression by GATA2 in liver cells. Mol Immunol 2020; 123: 32-39.
6. Luo N, Cai Y, Zhang J, Tang W, Slagle BL, Wu X, et al. The C-terminal region of the hepatitis B virus X protein is required for its stimulation of HBV replication in primary mouse hepatocytes. Virus Res 2012; 165: 170-178.
7. Zhu Z, Zhu M-h. Enigmatic X gene of hepatitis B virus and its association with hepatocellular carcinoma. Zhonghua Bing Li Xue Za Zhi 2006; 35: 423-426.
8. Zhou YM, Cao L, Li B, Zhang XZ, Yin ZF. Expression of HBx protein in hepatitis B virus-infected intrahepatic cholangiocarcinoma. Hepatobiliary Pancreat Dis Int 2012; 11: 532-535.
9. Shen Z, Wu J, Gao Z, Wang J, Zhu H, Mao R, et al. Characterization of IL-21-expressing recombinant hepatitis B virus (HBV) as a therapeutic agent targeting persisting HBV infection. Theranostics 2020; 10: 5600-5612.
10. Zhu K, Huang W, Wang W, Liao L, Li S, Yang S, et al. Up-regulation of S100A4 expression by HBx protein promotes proliferation of hepatocellular carcinoma cells and its correlation with clinical survival. Gene 2020; 749: 144679.
11. Yan J, Yao Z, Hu K, Zhong Y, Li M, Xiong Z, et al. Hepatitis B virus core promoter A1762T/G1764A (TA)/T1753A/T1768A mutations contribute to hepatocarcinogenesis by deregulating Skp2 and P53. Dig Dis Sci 2015; 60: 1315-1324.
12. Enomoto H, Aizawa N, Nishikawa H, Ikeda N, Sakai Y, Takata R, et al. Relationship between hepatic steatosis and the elevation of aminotransferases in HBV-infected patients with HBe-antigen negativity and a low viral load. Medicine (Baltimore) 2016; 95(17): e3565.
13. Liu CJ, Chen BF, Chen PJ, Lai MY, Huang WL, Kao JH, et al. Role of hepatitis B viral load and basal core promoter mutation in hepatocellular carcinoma in hepatitis B carriers. J Infect Dis 2006; 193: 1258-1265.
14. Li W, Goto K, Matsubara Y, Ito S, Muroyama R, Li Q, et al. The characteristic changes in hepatitis B virus x region for hepatocellular carcinoma: a comprehensive analysis based on global data. PLoS One 2015; 10(5): e0125555.
15. Xie Y, Li M, Wang Y, Hofschneider PH, Weiss L. Site-specific mutation of the hepatitis B virus enhancer II B1 element: effect on virus transcription and replication. J Gen Virol 2001; 82: 531-535.
16. Murakami S, Cheong JH, Kaneko S. Human hepatitis virus X gene encodes a regulatory domain that represses transactivation of X protein. J Biol Chem 1994; 269: 15118-15123.
17. Lizzano RA, Yang B, Clippinger AJ, Bouchard MJ. The C-terminal region of the hepatitis B virus X protein is essential for its stability and function. Virus Res 2011; 155: 231-239.
18. Kumar M, Jung SY, Hodgson AJ, Madden CR, Qin J, Slagle BL. Hepatitis B virus regulatory HBx protein binds to adaptor protein IPS-1 and inhibits the activation of beta interferon. J Virol 2011; 85: 987-995.
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IssueVol 14 No 4 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v14i4.10242
Keywords
Hepatitis B virus; X protein; Infections; Enhancer II; Mutation; Liver diseases

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How to Cite
1.
Karami C, Mollaei H, Arabzadeh SA, Mazloum Jalali K, Amerkani S, Pashangzadeh S, Nikpour N. The mutations frequency of enhancer II/HBx regions of hepatitis B virus in acutely infected Iranian patients: a cross-sectional study. Iran J Microbiol. 2022;14(4):554-562.