Institute of Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, Essen, Germany.
J Virol. 2013 Mar;87(5):2956-62. doi: 10.1128/JVI.03081-12. Epub 2012 Dec 26.
Hepatitis C virus (HCV) is considered to have a causative role in B-cell lymphoproliferative diseases, including B-cell lymphomas, in chronic virus carriers. Previous data from in vitro HCV-infected B-cell lines and peripheral blood mononuclear cells from HCV-positive individuals suggested that HCV might have a direct mutagenic effect on B cells, inducing mutations in the tumor suppressor gene TP53 and the proto-oncogenes BCL6 and CTNNB1 (β-catenin). To clarify whether HCV indeed has a mutagenic effect on B cells in vivo, we analyzed naive and memory B cells from the peripheral blood of four chronic HCV carriers and intrahepatic B cells from the livers of two HCV-positive patients for mutations in the three reported target genes. However, no mutations were found in the TP53 and CTNNB1 genes. For BCL6, which is a physiological target of the somatic hypermutation process in germinal-center B cells, the mutation levels identified were not higher than those reported in the respective B-cell subsets in healthy individuals. Hence, we conclude that in chronic HCV carriers, the virus does not generally induce mutations in the cancer-related genes TP53, CTNNB1, and BCL6 in B cells. Based on these findings, new targets have to be investigated as potential mediators of HCV-associated B-cell lymphomagenesis.
丙型肝炎病毒（HCV）被认为在慢性病毒携带者的 B 细胞淋巴瘤等 B 细胞淋巴增殖性疾病中起致病作用。先前来自 HCV 感染的 B 细胞系和 HCV 阳性个体外周血单个核细胞的体外数据表明，HCV 可能对 B 细胞具有直接的诱变作用，导致肿瘤抑制基因 TP53 和原癌基因 BCL6 和 CTNNB1（β-连环蛋白）发生突变。为了阐明 HCV 是否确实对体内 B 细胞具有诱变作用，我们分析了来自四名慢性 HCV 携带者外周血的幼稚 B 细胞和记忆 B 细胞以及两名 HCV 阳性患者肝脏内的 B 细胞，以检测三个报道的靶基因中的突变。然而，在 TP53 和 CTNNB1 基因中没有发现突变。对于 BCL6，它是生发中心 B 细胞体细胞超突变过程的生理靶标，鉴定的突变水平并不高于健康个体中相应 B 细胞亚群报道的水平。因此，我们得出结论，在慢性 HCV 携带者中，病毒通常不会诱导 B 细胞中与癌症相关的基因 TP53、CTNNB1 和 BCL6 发生突变。基于这些发现，必须研究新的靶标作为 HCV 相关 B 细胞淋巴瘤发生的潜在介质。
