Mingze Su1, Kuanhui Xiang1, Yao Li1, Yutang Li1, Juan Deng1, Xizhan Xu1, Ling Yan1, Hui Zhuang2, Tong Li3. 1. Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. 2. Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address: zhuangbmu@126.com. 3. Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address: tongli08@vip.sina.com.
Abstract
OBJECTIVES: Hepatitis B virus (HBV) subgenotype B2 is prevalent in China and some other parts of Asia. This study aimed to carry out a subgenotype B2 specific mutation analysis on important amino acid (AA) sites in overlapping reverse transcriptase (RT) and surface (S) protein coding regions of HBV. MATERIALS AND METHODS: A total of 143 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with HBV subgenotype B2 infection were enrolled. HBV RT/S regions were sequenced focusing on 43 RT resistance AA sites and 31 S AA sites with functional/structural/conformational importance. RESULTS: According to the consensus AA sequence for subgenotype B2, 49.7% (71/143) of RT and 33.6% (48/143) of S protein sequences contained detectable substitutions at 58.1% (25/43) of studied AA sites in RT and 51.6% (16/31) of AA sites in S proteins, respectively. The most frequently detected substitutions were rtN134D/S (44/143, 30.8%) and sT126A/S (22/143, 15.4%), which were located in the RT A-B interdomain region and the corresponding antigenicity determinant region of S protein, respectively. In addition, two patients harboring drug resistance mutations rtL80V+rtM204I and rtL180M+rtM204V were found. Interestingly, the patients with detectable AA substitutions at any of the 74 sites in either/both of RT/S sequences had significantly lower serum HBV DNA and HBsAg levels than that in patients without detectable RT/S AA substitutions (P<0.05). A trend Chi-squared test indicated that a negative association of serum HBsAg level with S protein sequence substitution rate was statistically significant (P=0.047). CONCLUSION: This subgenotype B2 specific mutation analysis revealed some naturally occurring hot spot substitutions at important AA sites of HBV RT/S proteins, which together might influence the serum HBV DNA and HBsAg levels in HBeAg-positive CHB patients.
OBJECTIVES:Hepatitis B virus (HBV) subgenotype B2 is prevalent in China and some other parts of Asia. This study aimed to carry out a subgenotype B2 specific mutation analysis on important amino acid (AA) sites in overlapping reverse transcriptase (RT) and surface (S) protein coding regions of HBV. MATERIALS AND METHODS: A total of 143 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with HBV subgenotype B2 infection were enrolled. HBV RT/S regions were sequenced focusing on 43 RT resistance AA sites and 31 S AA sites with functional/structural/conformational importance. RESULTS: According to the consensus AA sequence for subgenotype B2, 49.7% (71/143) of RT and 33.6% (48/143) of S protein sequences contained detectable substitutions at 58.1% (25/43) of studied AA sites in RT and 51.6% (16/31) of AA sites in S proteins, respectively. The most frequently detected substitutions were rtN134D/S (44/143, 30.8%) and sT126A/S (22/143, 15.4%), which were located in the RT A-B interdomain region and the corresponding antigenicity determinant region of S protein, respectively. In addition, two patients harboring drug resistance mutations rtL80V+rtM204I and rtL180M+rtM204V were found. Interestingly, the patients with detectable AA substitutions at any of the 74 sites in either/both of RT/S sequences had significantly lower serum HBV DNA and HBsAg levels than that in patients without detectable RT/S AA substitutions (P<0.05). A trend Chi-squared test indicated that a negative association of serum HBsAg level with S protein sequence substitution rate was statistically significant (P=0.047). CONCLUSION: This subgenotype B2 specific mutation analysis revealed some naturally occurring hot spot substitutions at important AA sites of HBV RT/S proteins, which together might influence the serum HBV DNA and HBsAg levels in HBeAg-positive CHB patients.
Authors: Kuan-Hui Xiang; Eleftherios Michailidis; Hai Ding; Ya-Qin Peng; Ming-Ze Su; Yao Li; Xue-En Liu; Viet Loan Dao Thi; Xian-Fang Wu; William M Schneider; Charles M Rice; Hui Zhuang; Tong Li Journal: J Hepatol Date: 2016-09-17 Impact factor: 25.083
Authors: Marina Campos-Valdez; Hugo C Monroy-Ramírez; Juan Armendáriz-Borunda; Laura V Sánchez-Orozco Journal: Viruses Date: 2021-06-18 Impact factor: 5.048