Number of mutations within CTL-defined epitopes of the hepatitis B Virus (HBV) core region is associated with HBV disease progression.
Number of mutations within CTL-defined epitopes of the hepatitis B Virus (HBV) core region is associated with HBV disease progression.
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DOI：
10.1002/jmv.22226
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发表时间：
2011-12
影响因子：
12.7
通讯作者：
Mehta, Sanjay
中科院分区：
文献类型：
--
作者：
Kim, Daniel;Lyoo, Kwang Soo;Smith, Davey;Hur, Wonhee;Hong, Sung Woo;Sung, Pil Soo;Yoon, Seung Kew;Mehta, Sanjay
与乙肝病毒(HBV)相关的进行性肝病的病毒学决定因素仍不清楚。以前的研究表明，乙肝病毒疾病与特定的突变有关，但这种关联可能会被乙肝病毒的基因型、感染者的人类白细胞抗原单倍型或两者兼而有之。研究了位于假定的细胞毒性T淋巴细胞导向表位(CDE)内的非同义突变与疾病状态之间的关系。从韩国首尔的临床队列中登记了感染乙肝病毒的受试者，并分析了与受试者人口统计学和乙肝病毒相关疾病状态相关的CDE内外的HBVc基因序列突变模式。没有特定的突变或突变模式与进展性疾病状态相关；然而，与HBe Ag阳性的慢性乙肝感染者相比，肝硬变和肝细胞癌患者CDE中非同义突变的数量更多(P分别为0.007和0.026)。总而言之，这项研究表明，病毒逃逸突变与病毒疾病进展有关，病毒逃逸突变是CTL活性的标志。这些数据表明，与任何单一突变或突变模式相比，乙肝病毒核心区非同义突变的数量可能更好地预测乙肝疾病的进展。
The virologic determinants of progressive liver disease associated with hepatitis B virus (HBV) remain unclear. Previous investigations have associated HBV disease with specific mutations but this association may be confounded by HBV genotype, HLA haplotype of the infected individual or both. The association between non-synonymous mutations located within putative cytotoxic T-lymphocyte directed epitopes (CDE) of the HBV core region and disease states was investigated. Subjects infected with HBV were enrolled from a clinical cohort in Seoul, Korea, and HBV core gene sequences were analyzed for mutational patterns inside and outside of CDE with respect to subject demographics and HBV-related disease states. No specific mutation or pattern of mutations were associated with progressive disease states; however, individuals with cirrhosis and hepatocellular carcinoma had greater numbers of non-synonymous mutations within CDE when compared to those with chronic HBV infection who were HBeAg positive (P = 0.007 and 0.026, respectively). In conclusion, this study demonstrates that HBV disease progression is associated with viral escape mutations that are a marker of CTL activity. These data suggest that the number of non-synonymous mutations in the HBV core region may predict HBV disease progression better than any single mutation or pattern of mutations.
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DOI：
10.1073/pnas.88.23.10445
发表时间：
1991-12-01
影响因子：
11.1
作者：
BERTOLETTI, A;FERRARI, C;CHISARI, FV
通讯作者：
CHISARI, FV
影响因子：
29.4
作者：
Kao, JH;Chen, PJ;Chen, DS
通讯作者：
Chen, DS
影响因子：
13.5
作者：
Bozkaya, H;Ayola, B;Lok, ASF
通讯作者：
Lok, ASF
影响因子：
5.4
作者：
Osiowy, Carla;Giles, Elizabeth;Minuk, Gerald Y.
通讯作者：
Minuk, Gerald Y.
DOI：
10.1093/jnci/djp180
发表时间：
2009-08-05
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Liu S;Zhang H;Gu C;Yin J;He Y;Xie J;Cao G
通讯作者：
Cao G