Deletions in the hepatitis B virus core gene may influence the clinical outcome in hepatitis B e antigen–positive asymptomatic healthy carriers
Deletions in the hepatitis B virus core gene may influence the clinical outcome in hepatitis B e antigen–positive asymptomatic healthy carriers
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乙型肝炎病毒核心基因的缺失可能会影响乙型肝炎e抗原阳性无症状健康携带者的临床结果
DOI：
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发表时间：
1998
影响因子：
12.7
通讯作者：
K. Ikeda
中科院分区：
文献类型：
--
作者：
A. Tsubota;H. Kumada;Kimiko Takaki;K. Chayama;Mizuho Kobayashi;M. Kobayashi;Yoshiyuki Suzuki;S. Saitoh;Y. Arase;N. Murashima;K. Ikeda
为了阐明慢性HBV感染中B型肝炎病毒（HBV）核心基因突变的意义，我们前瞻性随访了HBe抗原阳性的无症状健康携带者，根据血清丙氨酸转氨酶（ALT）浓度记录了他们的疾病发作，并连续分析了慢性感染从静止期到活动期的血清样本。在3名女性携带者中，在随访期间记录了首次发作。通过聚合酶链反应、克隆和HBV前C/核心开放阅读框基因组测序的系列分析表明，在2例患者中，核心基因缺失的克隆在静止期出现，随后在活动期持续存在，这些患者未能血清转化为抗-HBe，尽管接受了干扰素（IFN）治疗，但ALT水平持续升高。缺失是多种多样的、重叠的，并且位于中间核心区域，范围从氨基酸（aa）位置64至128。其余1例患者在IFN治疗后发生血清转化，在随访期间没有核心基因缺失HBV变异，但在一些限制性核心区域聚集了aa取代。两名对照无症状携带者，在15至19年的时间内生化或病毒学标志物没有变化，没有核心基因缺失变异和很少的aa变化。这些发现表明，即使在静止期，核心基因的中间部分也会缺失。因此，宿主和病毒之间的免疫相互作用可能是隐性的，并且在静止期出现的核心基因缺失HBV变异体可能参与肝炎的发作和随后的慢性感染结局。J. Med. Virol. 56：287-293，1998.© 1998 Wiley利斯公司
To address the significance of mutations within the hepatitis B virus (HBV) core gene in chronic HBV infection, we followed prospectively HBe‐antigen–positive asymptomatic healthy carriers, documented the onset of their disease based on serum alanine transaminase (ALT) concentrations, and analyzed sequentially serum samples from a quiescent phase through to an active phase of the chronic infection. In three female carriers, the first flare‐up was documented during the follow‐up period. Serial analysis by polymerase chain reaction, cloning, and sequencing of the HBV precore/core open reading frame genome demonstrated that clones with core gene deletions emerged during the quiescent phase and persisted subsequently during the active phase in two patients, who failed to seroconvert to anti‐HBe and had persistently increased ALT levels despite interferon (IFN) therapy. The deletions were various, overlapping, and located in the mid‐core region ranging from amino acid (aa) position 64 to 128. The remaining patient, who seroconverted with IFN therapy, did not have a core‐gene‐deletion HBV variant during follow‐up, but had aa substitutions clustered in some restricted core regions. Two control asymptomatic carriers, who had no change in biochemical or virologic markers over a 15‐ to 19‐year period, had no core‐gene‐deletion variants and few aa changes. These findings indicate that the mid‐portion of the core gene is subject to deletion even during the quiescent phase. Thus, the immunologic interaction between the host and virus may occur insidiously, and the emergence of a core‐gene‐deletion HBV variant during the quiescent phase may be involved in the onset of hepatitis and the subsequent outcome of chronic infection. J. Med. Virol. 56:287–293, 1998. © 1998 Wiley‐Liss, Inc.
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影响因子：
7.8
作者：
DeKruyff, R H;Rizzo, L V;Umetsu, D T
通讯作者：
Umetsu, D T
DOI：
10.1073/pnas.85.22.8405
发表时间：
1988-11-01
影响因子：
11.1
作者：
STANDRING, DN;OU, JH;RUTTER, WJ
通讯作者：
RUTTER, WJ
抑制病毒复制的乙型肝炎病毒核心突变体的表征。
影响因子：
3.7
作者：
Scaglioni,PP;Melegari,M;Wands,JR
通讯作者：
Wands,JR
克隆的肝内乙型肝炎病毒核蛋白特异性辅助 T 细胞系的功能特征。
DOI：
--
发表时间：
1987
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ferrari,C;Mondelli,MU;Penna,A;Fiaccadori,F;Chisari,FV
通讯作者：
Chisari,FV