In vitro investigation of HBV clinical isolates from Chinese patients reveals that genotype C isolates possess higher infectivity than genotype B isolates

作     者：Tingting Liu Anlei Liu Yong Liu Shan Cen Quan Zhang Tingting Liu;Anlei Liu;Yong Liu;Shan Cen;Quan Zhang

作者机构：Department of Transfusion MedicineNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008China Department of Emergency MedicinePeking Union Medical College HospitalChinese Academy of Medical ScienceBeijing100730China Department of Laboratory MedicineNanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular MedicineThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008China Institute of Medicinal BiotechnologyChinese Academy of Medical ScienceBeijing100050China Department of Infectious DiseasesNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2022年第37卷第3期

页      面：398-407页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：supported by grants of the National Youth Natural Science Foundation of China,China(82102380) the Youth Natural Science Foundation of Jiangsu Province(BK20200126) the National Youth Natural Science Foundation of China,China(81602400)。 

主　　题：Hepatitis B virus(HBV) Genotype B Genotype C Clinical isolates Infectivity sL21S 

摘      要：Hepatitis B virus(HBV)genotype B and C are two major genotypes that are prevalent in Asia and differ in natural history and disease progression.The impact of HBV genotypes on viral replication and protein expression has been explored by the transfection of hepatoma cells with replication-competent HBV DNA,which mimics the later stages of the viral life cycle.However,the influence of HBV genotypes on the early events of viral infection remains undetermined,mainly due to the difficulties in obtaining sufficient infectious viral particles for infection assays.Here,we report that a high-titer HBV inoculum can be generated from the transient transfection-based cell model after optimizing transfection conditions and modifying the HBV-expressing construct.By performing in vitro infection assays using transiently transfected derived viruses,we found that clinical genotype C isolates possessed higher infectivity than genotype B isolates.Moreover,we identified a naturally occurring mutation sL21S in small hepatitis B surface protein,which markedly decreased the infectivity of HBV genotype C isolates,but not that of genotype B isolates.In summary,using infectious viral particles provided by the optimized transient transfection-based cell model,we have been able to investigate a wide range of HBV variants on viral infectivity,which may contribute to our understanding of the reasons for different clinical outcomes in HBV infections and the development of therapeutic drugs targeting the early stages of HBV life cycle.