Impact of topological regions of small hepatitis B virus surface antigen on its expression and secretion
SHEN Zhongliang1,2,*, RAO Yuliang3,*, WANG Wei2, MA Zhangmei2, LIU Jing1,2, PAN Shaokun2,4, XIE Youhua1,2
1. Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China; 2. Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; 3. School of Basic Medicine, Shanghai University of Medicine and Health Science, Shanghai 201318, China; 4. Department of Preventive Dentistry, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Abstract:The small hepatitis B virus surface antigen (SHB) is expressed on the endoplasmic reticulum (ER) and is secreted along the cellular secretory pathway. To analyze the impact of SHB domains on its expression and secretion, SHB proteins of eight HBV genotypes (A-H) plus a clinical strain C8 were subjected to a domain analysis. All the SHBs have four transmembrane motifs (Tmhelix1-4), three regions in the ER lumen (Inside1-3), and two regions outside of the ER (Outside1-2). The topological regions of SHBs in C8 and genotypes A, B, C, D, E and G were identical, while four topological regions of SHBs in genotypes F and H were slightly different from that in C8. Deletion analysis of SHB topological regions in C8 indicated that Inside1 region was not required for SHB expression and secretion; Outside1, Tmhelix2 and Inside2 regions were required for both SHB expression and secretion; Tmhelix1 and Outside2 regions were dispensable for SHB expression but needed for SHB secretion; Tmhelix3 and Tmhelix4 regions were important for SHB expression and necessary for SHB secretion. Finer deletion (6 amino acids) mapping in Outside1 and Outside2 regions showed that amino acids 55-78 of Outside1 and Outside2 were required for SHB secretion. This is the first systematic analysis of the impact of SHB topological regions on SHB expression and secretion, which has provided valuable clues for future study of the structure-function relationship of SHB.
沈忠良1,2,*,饶玉良3,*,王葳2, 马张妹2,刘晶1,2,潘少坤2,4,谢幼华1,2. 乙型肝炎病毒小表面抗原各拓扑区段对其表达和分泌的影响[J]. 微生物与感染, 2016, 11(5): 278-286.
SHEN Zhongliang1,2,*, RAO Yuliang3,*, WANG Wei2, MA Zhangmei2, LIU Jing1,2, PAN Shaokun2,4, XIE Youhua1,2. Impact of topological regions of small hepatitis B virus surface antigen on its expression and secretion. JOURNAL OF MICROBES AND INFECTIONS, 2016, 11(5): 278-286.