title: Higher detection rates of amino acid substitutions in HBV reverse transcriptase/surface protein overlapping sequence is correlated with lower serum HBV DNA and HBsAg levels in HBeAg-positive chronic hepatitis B patients with subgenotype B2.
abstract: 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.
authors.affiliation: 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.
authors.forename: Mingze
authors.initials: M
authors.lastname: Su
authors.affiliation: 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.
authors.forename: Kuanhui
authors.initials: K
authors.lastname: Xiang
authors.affiliation: 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.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yutang
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Xizhan
authors.initials: X
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: 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.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000097:blood / Q000276:immunology; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D004279:DNA, Viral; D005260:Female; D023061:Gene Order; D016679:Genome, Viral; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000097:blood* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D012194:RNA-Directed DNA Polymerase
keywords: Hepatitis B virus; Reverse transcriptase; Subgenotype B2; Substitution; Surface protein