Amino acid substitutions at the positions 122 and 145 of hepatitis B surface ant

StephenW

J Virol. 2012 Feb 1. [Epub ahead of print]
Amino acid substitutions at the positions 122 and 145 of hepatitis B surface antigen (HBsAg) determine the antigenicity and immunogenicity of HBsAg and influence in vivo HBsAg clearance.Wu C, Deng W, Deng L, Cao L, Qin B, Li S, Wang Y, Pei R, Yang D, Lu M, Chen X.
SourceWuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

AbstractA variety of amino acid (8) substitutions such as K122I and G145R have been identified around or within the "a" determinant of hepatitis B surface antigen (HBsAg), impair HBsAg secretion and antibody binding and may be responsible for immune escape in patients. In this study, we examined how different substitutions at aa positions 122 and 145 of HBsAg influence HBsAg expression, secretion, and recognition by anti-HBs antibodies. The results showed that the hydrophobicity, the presence of the phenyl group, and the charges in the side chain of the aa residues at position 145 reduced HBsAg secretion and impaired reactivity with anti-HBs antibodies. Only the substitution K122I at the position 122 affected HBsAg secretion and recognition by anti-HBs antibodies. Genetic immunization in mice demonstrated that priming of anti-HBs antibody response was strongly impaired by the substitutions K122I, G145R, and others like G145I, G145W, and G145E. Mice preimmunized with wtHBsAg or variant HBsAg (vtHBsAg) were challenged by hydrodynamic injection (HI) with a replication competent hepatitis B virus (HBV) clone. HBsAg persisted in peripheral blood for at least 3 days after HI in mice preimmunized with vtHBsAg but undetectable in mice preimmunized with wtHBsAg indicating vtHBsAg may fail to induce proper immune responses for efficient HBsAg clearance. In conclusion, the biochemical properties of aa residues at positions 122 and 145 of HBsAg have a major impact on the antigenicity and immunogenecity. In addition, the presence of proper anti-HBs antibodies is indispensable for neutralization and clearance of HBsAg during HBV infection.





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StephenW

J病毒学。 2012年二月1。
在B型肝炎表面抗原（HBsAg）的位置122和145氨基酸换人决定HBsAg和影响力在体内HBsAg清除的抗原性和免疫原性。
，曹武，邓W，邓小平大号大号，秦乙，李曙光，王元，裴ŕ，杨ð，露米，陈旭
源

武汉病毒研究所，中国科学院，武汉，中国。
抽象

K122I和G145R变异如一个多种氨基酸（8）替换已确定周围或在“一个”乙肝表面抗原（HBsAg）的行列式，损害HBsAg的分泌和抗体结合，可能是负责患者的免疫逃逸。在这项研究中，我们研究了不同的换人如何在122和145对HBsAg的影响AA位置HBsAg的表达，分泌，抗-HBs抗体的认可。结果表明，疏水性，苯环的存在，在145位氨基酸残基侧链的收费减少HBsAg的分泌和抗-HBs抗体反应受损。只有在122的位置受影响HBsAg的分泌和抗-HBs抗体识别的替代K122I。在小鼠的遗传免疫证明，抗-HBs抗体反应引发了强烈K122I的换人，G145R变异，以及其他像G145I，G145W，G145E受损。小鼠preimmunized与wtHBsAg或变异乙肝表面抗原（vtHBsAg）流体力学注射复制主管乙型肝炎病毒（HBV）克隆（您好）的挑战。乙肝表面抗原持续至少3天，后在小鼠，在小鼠preimmunized与wtHBsAg表明vtHBsAg可能会失败，导致适当的免疫反应，高效的HBsAg清除vtHBsAg但检测不到preimmunized您好外周血。总之，HBsAg的位置122和145氨基酸残基在生化特性有重大影响的抗原性和免疫原性。此外，适当的抗-HBs抗体的存在是不可缺少的中和在乙肝病毒感染乙肝表面抗原的清除。