Complementation of Wild-Type and Drug-Resistant Hepatitis B Virus Genomes to Maintain Viral Replication and Rescue Virion Production under Nucleos(t)ide Analogs  

作　　者：Chunchen Wu Baolin Li Xiaoyong Zhang Kaitao Zhao Yingshan Chen Yifei Yuan Yan Liu Rongjuan Chen Dongping Xu Xinwen Chen Mengji Lu 

机构地区：[1]Department of Laboratory Medicine,Maternal and Child Health Hospital of Hubei Province,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430070,China [2]State Key Lab of Virology,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430071,China [3]Institute of Virology,University Hospital of Essen,45122 Essen,Germany [4]University of Chinese Academy of Sciences,Beijing 100049,China [5]Institute of Infectious Diseases and Liver Failure Research Center,Beijing 302 Hospital,Beijing 100039,China

出　　处：《Virologica Sinica》2019年第4期377-385,共9页中国病毒学（英文版）

基　　金：supported by the Deutsche Forschungsgemeinschaft (TRR60);the National Nature Science Foundation of China (31770180, 31621061);the Youth Innovation Promotion Association CAS (No. 2016303);the Youth Planning Project of Hubei Health Planning Commission (WJ2017Q027)

摘　　要：As the open reading frames of hepatitis B virus(HBV)genomes are overlapping,resistance mutations(MTs)in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins,which are usually detected as a mixed population with wild-type(WT)HBV.The question was raised how the coexistence of nucleos(t)ide analogs(NAs)resistance MTs and WT sequences affects HBV replication.In the present study,HBV genomes with frequently detected reverse transcriptase(RT)/surface truncation MTs,rtA181T/sW172^*,rtV191I/sW182^*and rtM204I/sW196^*,were phenotypically characterized alone or together with their WT counterparts in different ratios by transient transfection in the absence or presence of Nas.In the absence of Nas,RT/surface truncation MTs impaired the expression and secretion of HBV surface proteins,and had a dose-dependent negative effect on WT HBV virion secretion.However,in the presence of Nas,coexistence of MTs with WT maintained viral replication,and the presence of WT was able to rescue the production of MT HBV virions.Our findings reveal that complementation of WT and MT HBV genomes is highly effective under drug treatment.As the open reading frames of hepatitis B virus(HBV) genomes are overlapping, resistance mutations(MTs) in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins, which are usually detected as a mixed population with wild-type(WT) HBV. The question was raised how the coexistence of nucleos(t)ide analogs(NAs) resistance MTs and WT sequences affects HBV replication. In the present study, HBV genomes with frequently detected reverse transcriptase(RT)/surface truncation MTs, rtA181T/sW172~*, rtV191I/sW182~* and rtM204I/sW196~*, were phenotypically characterized alone or together with their WT counterparts in different ratios by transient transfection in the absence or presence of NAs. In the absence of NAs, RT/surface truncation MTs impaired the expression and secretion of HBV surface proteins, and had a dose-dependent negative effect on WT HBV virion secretion. However, in the presence of NAs,coexistence of MTs with WT maintained viral replication, and the presence of WT was able to rescue the production of MT HBV virions. Our findings reveal that complementation of WT and MT HBV genomes is highly effective under drug treatment.

关 键 词：Hepatitis B virus(HBV) Viral replication Nucleos(t)ide ANALOGS resistance mutations Surface truncation mutation 

分 类 号：Q[生物学]