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Bioinformatic determination of dominant amino acid sequence and mutation hotspots in hepatitis B virus X protein |
WANG Wei1, HE Yonggang1, PU Yonglan2, PAN Shaokun1,3, XIE Youhua1 |
1. Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; 2. Department of Infectious Diseases, Taicang First People’s Hospital, Taicang 215400, China; 3. Shanghai Keybiomed Technology Co., Ltd. Shanghai 201206, China |
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Abstract Hepatitis B virus X protein (HBx), a 154-amino acid protein encoded by hepatitis B virus (HBV), has been implicated in the development of hepatocellular carcinoma (HCC). The aim of the present study is to establish a complete and dominant peptide sequence of HBx. A total of 13 950 HBx protein sequences were retrieved from GenBank. After excluding the non-complete ones that harbor insertions, deletions and non-methionine start amino acid, 7 126 were included in the study. Occurrence frequencies of the 20 amino acids at each position of HBx were calculated. The amino acid with the highest frequency at each position was designated as the dominant amino acid at the position and all the dominant residues constituted the complete and dominant peptide sequence of HBx. All the non-dominant amino acids were taken as the mutants. 32 hotspots with a mutation rate over 10.0% were detected. The positions 36, 42, 44, 87, 88, and 127 showed a higher polymorphism, having more than 4 kinds of mutations with a rate over 1.0%. The K130M/V131I dual mutation, regarded as a high risk factor of HBV-related HCC, showed an occurrence frequency at 34.7% in this study. The homology between the dominant sequence and each of the 7 126 HBx sequences was calculated. 50 sequences, which included 2 sequences with a homology to the dominant below 75% and 48 sequences with a homology between 76%-99%, were chosen for phylogenetic tree construction. The phylogenetic tree with the dominant HBx, 50 selected HBx and 23 reference sequences showed that the dominant HBx belonged to genotype C. This study has systematically constituted a calculated HBx peptide sequence with dominant amino acid at each position, laying the foundation for the basic and applied research on HBx.
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Received: 05 April 2016
Published: 25 December 2016
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Corresponding Authors:
PAN Shaokun, XIE Youhua
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