Abstract:
BACKGROUND:Vaccine-escaped hepatitis B virus (HBV) mutations occur within the "a" determinant area, which is located in the major hydrophilic region (MHR) of the hepatitis B surface antigen (HBsAg) protein. It is now well established that the common G145R mutation is highly capable of escaping from HBsAg immune recognition. However, the impacts of this mutation on the structure and immunogenic activity of HBsAg have been poorly investigated. OBJECTIVES:The present study analyzed the effects of the G145R mutation on the structure and immunogenic activity of the HBsAg. MATERIALS AND METHODS:Three-dimensional (3D) structure of HBsAg for both the wild-type and G145R mutant were predicted and refined using several web tools. After quantitative evaluations, the effects of the G145R mutation on the secondary and 3D structures of the HBsAg were investigated. In parallel, the immunogenic activity of the wild-type and mutant HBsAg was also analyzed using a ClusPro docking server as well as the IEDB web tool. Further analyses were performed via molecular dynamics (MD) simulations using the GROMACS v5.0.2 simulation package. RESULTS:The G145R mutation causes a considerable reduction in the immunogenic activity of the HBsAg through a conformational change in the HBsAg antigenic loops. This mutation inserts a new β-strand in the "a" determinant region of the HBsAg, leading to a reduced binding affinity to its monoclonal antibody, MAb12. The G145R mutation also increased the compactness and stability of the HBsAg by enhancing the rigidity of the "a" determinant. CONCLUSIONS:These data will be beneficial for designing more advanced antibodies for the recognition of the HBsAg in diagnostics. In addition, the results of this study may assist in the design or development of more effective hepatitis B vaccines.
journal_name
Hepat Monjournal_title
Hepatitis monthlyauthors
Rezaee R,Poorebrahim M,Najafi S,Sadeghi S,Pourdast A,Alavian SM,Alavian SE,Poortahmasebi Vdoi
10.5812/hepatmon.39097subject
Has Abstractpub_date
2016-06-28 00:00:00pages
e39097issue
7eissn
1735-143Xissn
1735-3408journal_volume
16pub_type
杂志文章abstract::Patients with chronic hepatitis B infection should be followed up to identify possible changes in disease status, such as HBsAg seronversion. There are little data on the outcome of such cases, and the response rate to HBV vaccine has not been discussed extensively. ...
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