Evolution of wild type and mutants of the YMDD motif of hepatitis B virus polymerase during lamivudine therapy

	Evolution of wild type and mutants of the YMDD motif of hepatitis B virus polymerase during lamivudine therapy
	Zhang, XX; Liu, CM; Gong, QM; Zhang, SY; Zhang, DH; Lu, ZM; Wang, YA
刊名	JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
	2003
卷号	18 期号:12 页码:1353-1357
关键词	hepatitis B virus lamivudine mutation YMDD motif
通讯作者	Zhang, XX (reprint author), Shanghai Med Univ 2, Rui Jin Hosp, Dept Infect Dis, Shanghai 200025, Peoples R China.,
英文摘要	Background and Aim: Long-term lamivudine treatment for chronic hepatitis B virus (HBV) infection induces the emergence of lamivudine resistant HBV YMDD mutant strains. The aim of the present study was to observe the clone evolution of YMDD wild type and mutant strains in pretreatment and post-treatment samples during lamivudine therapy and analyze their clinical significance. Methods: Ten serum samples (five before and five after 48 weeks of therapy) obtained from five patients chronically infected with HBV and treated with lamivudine were studied. Part of the HBV polymerase gene flanking the YMDD motif was sequenced after polymerase chain reaction (PCR) amplification. Meanwhile, 20-24 clones were selected at random from each sample and YMDD wild type and mutant strains were detected by real-time fluorimetry PCR established in our laboratory. Results: The YMDD mutants were not detectable in all five patients before treatment and were found in four patients after 48 weeks of therapy by sequencing directly on PCR products. Analysis of individual clones showed that the ratios of mutant strains in each of the five patients were 0, 9.5, 0, 4.5 and 5.6%, respectively, before therapy and 100, 100, 65, 100 and 0%, respectively, after 48 weeks of therapy. M552I was detected before therapy in one patient but M552V became the domain strain after therapy. Until 52 weeks of therapy, serum HBV DNA and alanine aminotransferase (ALT) breakthrough were found in two of the four patients with YMDD mutations. The fifth patient experienced breakthrough of ALT but HBV DNA remained undetectable. Conclusions: The mutant strains of YMDD motif of HBV polymerase could be found in patients before lamivudine treatment, indicating that antiviral therapy allows the rapid selection of resistant strains. The replication ability of the M552V mutant strain might be stronger than that of the M552I mutant strain. (C) 2003 Blackwell Publishing Asia Pty Ltd.
学科主题	Gastroenterology & Hepatology
类目[WOS]	Gastroenterology & Hepatology
关键词[WOS]	REVERSE-TRANSCRIPTASE ; RESISTANCE ; MUTATIONS ; IDENTIFICATION ; REPLICATION ; INFECTION
收录类别	SCI
语种	英语
WOS记录号	WOS:000186698300004
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2369]
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	Zhang, XX,Liu, CM,Gong, QM,et al. Evolution of wild type and mutants of the YMDD motif of hepatitis B virus polymerase during lamivudine therapy[J]. JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY,2003,18(12):1353-1357.
APA	Zhang, XX.,Liu, CM.,Gong, QM.,Zhang, SY.,Zhang, DH.,...&Wang, YA.(2003).Evolution of wild type and mutants of the YMDD motif of hepatitis B virus polymerase during lamivudine therapy.JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY,18(12),1353-1357.
MLA	Zhang, XX,et al."Evolution of wild type and mutants of the YMDD motif of hepatitis B virus polymerase during lamivudine therapy".JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 18.12(2003):1353-1357.