A single amino acid in the reverse transcriptase domain of hepatitis B virus affects virus replication efficiency

	A single amino acid in the reverse transcriptase domain of hepatitis B virus affects virus replication efficiency
	Lin, X; Yuan, ZH; Wu, L; Ding, JP; Wen, YM
刊名	JOURNAL OF VIROLOGY
	2001
卷号	75 期号:23 页码:11827-11833
通讯作者	Wen, YM (reprint author), Fudan Univ, Med Ctr, Dept Mol Virol, 138 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China.,
英文摘要	To explore functional domains in the hepatitis B virus (HBV) polymerase, two naturally occurring HBV isolates (56 and 2-18) with 98.7% nucleic acid sequence homology but different replication efficiencies were studied. After transfection into HepG2 cells, HBV DNA isolated from intracellular virus core particles was much higher in 56-transfected cells than in cells transfected with 2-18. The structural basis for the difference in replication efficiency between these two isolates was studied by functional domain gene substitution. The complete polymerase (P) gene and its gene segments coding for the terminal protein (TP), spacer (SP), reverse transcriptase (RT), and RNase H in 2-18 were separately replaced with their counterparts from 56 to construct full-length chimeric genomes. Cell transfection analysis revealed that substitution of the complete P gene of 2-18 with the P gene front 56 slightly enhanced viral replication. The only chimeric genome that regained the high replication efficiency of the original 56 isolate was the one with substitution of the RT gene of 2-18 with that from 56. Within the RT region, amino acid differences between isolates 2-18 and 56 were located at positions 617 (methionine versus leucine), 652 (serine versus proline), and 682 (valine versus leucine). Point mutation Identified amino acid 652 as being responsible for the difference in replication efficiency. Homologous modeling studies of the HBV RT domain suggest that the mutation of residue 652 from proline to serine might affect the conformation of HBV RT which interacts with the template-primer, leading to impaired polymerase activity.
学科主题	Virology
类目[WOS]	Virology
关键词[WOS]	DEPENDENT RNA-POLYMERASE ; CRYSTAL-STRUCTURE ; C VIRUS ; GENE ; EXPRESSION ; FRAGMENT ; PRIMER
收录类别	SCI
语种	英语
WOS记录号	WOS:000172033100059
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2716]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Lin, X,Yuan, ZH,Wu, L,et al. A single amino acid in the reverse transcriptase domain of hepatitis B virus affects virus replication efficiency[J]. JOURNAL OF VIROLOGY,2001,75(23):11827-11833.
APA	Lin, X,Yuan, ZH,Wu, L,Ding, JP,&Wen, YM.(2001).A single amino acid in the reverse transcriptase domain of hepatitis B virus affects virus replication efficiency.JOURNAL OF VIROLOGY,75(23),11827-11833.
MLA	Lin, X,et al."A single amino acid in the reverse transcriptase domain of hepatitis B virus affects virus replication efficiency".JOURNAL OF VIROLOGY 75.23(2001):11827-11833.