乙型肝炎病毒X蛋白（HBx）对γ疱疹病毒癌基因启动子的转录激活作用。

Transcriptional activation of gammaherpesviral oncogene promoters by the hepatitis B viral X protein (HBx).

作者信息

Assogba Barnabe Dossou, Paik Nak Whan, Rho Hyune Mo

机构信息

Indang Institute of Molecular Biology, Inje University, Seoul 100-032, Korea.

出版信息

DNA Cell Biol. 2004 Mar;23(3):141-8. doi: 10.1089/104454904322964733.

DOI:10.1089/104454904322964733

PMID:15068583

Abstract

The latent membrane protein-1 (LMP1) of Epstein-Barr Virus (EBV), saimiri transformation protein (STP) of Herpesvirus saimiri (HVS), and K1 protein of Kaposi's sarcoma-associated herpesvirus (KSHV) are potent gammaherpesvirus oncogenes. To study the possible effects of double viral infection, we investigated the effects of oncogenic early proteins of DNA viruses E1A and E1B (adenovirus-5), E6 and E7 (human papillomavirus-16), HBx (hepatitis B virus), Tag (SV40), and gammaherpesviral oncogene during co-infection in human B-lymphoma (Ramos) and human T-cell leukemia (Jurkat) cell lines. HBx transactivated the promoters of LMP1, STP, and K1 the most, by about six-, three-, and twofold, respectively. Analyses of site-directed mutation and the heterologous promoter system showed that HBx activated the promoter activity of these genes via the NF-kappaB site. These results suggest that HBV (HBx) infection of cells previously infected by gammaherpesviruses transactivates their oncogenes, resulting in possible virus-related disease pathogenesis.

摘要

爱泼斯坦 - 巴尔病毒（EBV）的潜伏膜蛋白1（LMP1）、猴疱疹病毒（HVS）的赛米里转化蛋白（STP）以及卡波西肉瘤相关疱疹病毒（KSHV）的K1蛋白都是强效的γ疱疹病毒癌基因。为了研究双重病毒感染的可能影响，我们调查了DNA病毒E1A和E1B（腺病毒5型）、E6和E7（人乳头瘤病毒16型）、HBx（乙型肝炎病毒）、Tag（SV40）的致癌早期蛋白以及γ疱疹病毒癌基因在人B淋巴瘤（拉莫斯）和人T细胞白血病（Jurkat）细胞系共感染过程中的作用。HBx对LMP1、STP和K1启动子的反式激活作用最强，分别约为6倍、3倍和2倍。定点突变分析和异源启动子系统分析表明，HBx通过NF-κB位点激活这些基因的启动子活性。这些结果表明，先前感染γ疱疹病毒的细胞被乙肝病毒（HBx）感染后会反式激活其癌基因，从而可能导致与病毒相关的疾病发病机制。