Su Mingze, Xiang Kuanhui, Li Yao, Li Yutang, Deng Juan, Xu Xizhan, Yan Ling, Zhuang Hui, Li Tong
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.
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.
Infect Genet Evol. 2016 Jun;40:275-281. doi: 10.1016/j.meegid.2016.03.019. Epub 2016 Mar 19.
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.
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.
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).
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.
乙肝病毒（HBV）B2亚基因型在中国及亚洲其他一些地区较为普遍。本研究旨在对HBV重叠逆转录酶（RT）和表面（S）蛋白编码区的重要氨基酸（AA）位点进行B2亚基因型特异性突变分析。
共纳入143例B2亚基因型HBV感染的乙肝e抗原（HBeAg）阳性慢性乙型肝炎（CHB）患者。对HBV RT/S区域进行测序，重点关注43个RT耐药AA位点和31个具有功能/结构/构象重要性的S AA位点。
根据B2亚基因型的一致AA序列，RT蛋白序列的49.7%（71/143）和S蛋白序列的33.6%（48/143）在RT研究的AA位点的58.1%（25/43）和S蛋白AA位点的51.6%（16/31）处含有可检测到的替换。最常检测到的替换是rtN134D/S（44/143，30.8%）和sT126A/S（22/143，15.4%），分别位于RT A - B结构域间区域和S蛋白相应的抗原决定簇区域。此外，还发现了两名携带耐药突变rtL80V + rtM204I和rtL180M + rtM204V的患者。有趣的是，RT/S序列中74个位点中任何一个位点有可检测到的AA替换的患者，其血清HBV DNA和HBsAg水平显著低于无RT/S AA替换检测的患者（P < 0.05）。趋势卡方检验表明血清HBsAg水平与S蛋白序列替换率呈负相关具有统计学意义（P = 0.047）。
该B2亚基因型特异性突变分析揭示了HBV RT/S蛋白重要AA位点的一些自然发生的热点替换，这些替换可能共同影响HBeAg阳性CHB患者的血清HBV DNA和HBsAg水平。
