Toita Riki, Kawano Takahito, Kang Jeong-Hun, Murata Masaharu
Riki Toita, Department of Biomaterials, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
World J Gastroenterol. 2015 Jun 28;21(24):7400-11. doi: 10.3748/wjg.v21.i24.7400.
Human hepatitis B virus (HBV) is a member of the family Hepadnaviridae, and causes acute and chronic infections of the liver. The hepatitis B surface antigen (HBsAg) contains the large (L), middle (M), and small (S) surface proteins. The L protein consists of the S protein, preS1, and preS2. In HBsAg, the preS domain (preS1 + preS2) plays a key role in the infection of hepatocytic cells by HBV and has several immunogenic epitopes. Based on these characteristics of preS, several preS-based diagnostic and therapeutic materials and systems have been developed. PreS1-specific monoclonal antibodies (e.g., MA18/7 and KR127) can be used to inhibit HBV infection. A myristoylated preS1 peptide (amino acids 2-48) also inhibits the attachment of HBV to HepaRG cells, primary human hepatocytes, and primary tupaia hepatocytes. Antibodies and antigens related to the components of HBsAg, preS (preS1 + preS2), or preS1 can be available as diagnostic markers of acute and chronic HBV infections. Hepatocyte-targeting delivery systems for therapeutic molecules (drugs, genes, or proteins) are very important for increasing the clinical efficacy of these molecules and in reducing their adverse effects on other organs. The selective delivery of diagnostic molecules to target hepatocytic cells can also improve the efficiency of diagnosis. In addition to the full-length HBV vector, preS (preS1 + preS2), preS1, and preS1-derived fragments can be useful in hepatocyte-specific targeting. In this review, we discuss the literature concerning the applications of the HBV preS domain in bio- and nanotechnology.
人类乙型肝炎病毒(HBV)是嗜肝DNA病毒科的成员,可引起肝脏的急性和慢性感染。乙型肝炎表面抗原(HBsAg)包含大(L)、中(M)和小(S)表面蛋白。L蛋白由S蛋白、前S1和前S2组成。在HBsAg中,前S结构域(前S1 + 前S2)在HBV感染肝细胞中起关键作用,并具有多个免疫原性表位。基于前S的这些特性,已开发出几种基于前S的诊断和治疗材料及系统。前S1特异性单克隆抗体(例如MA18/7和KR127)可用于抑制HBV感染。一种肉豆蔻酰化的前S1肽(氨基酸2 - 48)也可抑制HBV与HepaRG细胞、原代人肝细胞和原代树鼩肝细胞的附着。与HBsAg、前S(前S1 + 前S2)或前S1的成分相关的抗体和抗原可作为急性和慢性HBV感染的诊断标志物。用于治疗分子(药物、基因或蛋白质)的肝细胞靶向递送系统对于提高这些分子的临床疗效以及减少它们对其他器官的不良反应非常重要。将诊断分子选择性递送至靶肝细胞也可提高诊断效率。除了全长HBV载体外,前S(前S1 + 前S2)、前S1和前S1衍生片段可用于肝细胞特异性靶向。在本综述中,我们讨论了有关HBV前S结构域在生物和纳米技术中应用的文献。