Hypermodification and immune escape of an internally deleted middle-envelope (M) protein of frequent and predominant hepatitis B virus variants
Hypermodification and immune escape of an internally deleted middle-envelope (M) protein of frequent and predominant hepatitis B virus variants
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DOI：
10.1006/viro.2001.1239
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发表时间：
2002-01-05
期刊：
影响因子：
3.7
通讯作者：
Shih, C
中科院分区：
文献类型：
--
作者：
Tai, PC;Suk, FM;Shih, C
在肝细胞癌（HCC）患者中经常发现人8型肝炎病毒（HBV）preS2区域内的天然缺失，而无肝硬化和HCC的慢性携带者不含可检测到的preS2缺失变体。我们的特点是两个不同的preS2内部缺失变异的两名患者。除了几种弱表型外，我们的研究还发现了三种意想不到的强表型：（1）观察到一种自相矛盾的“过度修饰”现象，其中含有preS2内部缺失的分泌的中（M）包膜蛋白的大小异质性和分子量显著增加。在瞬时转染人肝癌Huh7细胞系以及稳定转染啮齿动物肝癌细胞系7777中观察到这种现象。(2)通过Western印迹分析和免疫荧光显微镜检测到所有三种包膜蛋白（大，中，小）的细胞内积累显着增加。(3)中间包膜蛋白与preS2的内部缺失，不承认在体外由一个假定的中和抗血清，这表明这些变体可以逃避体内免疫识别。据我们所知，这是HBV自然感染中M缺失变异蛋白的首次鉴定和表征。(C)2002年，Elsevier Science。
Naturally occurring deletions within the human hepatitis 8 virus (HBV) preS2 region have frequently been identified in patients with hepatocellular carcinoma (HCC), while chronic carriers without cirrhosis and HCC contain no detectable preS2 deletion variants. We have characterized two different preS2 internal deletion variants from two patients. In addition to several weak phenotypes, our study revealed three unexpected strong phenotypes: (1) a paradoxical "hypermodification" phenomenon was observed with significantly increased size heterogeneity and molecular weights of the secreted middle (M) envelope proteins containing a preS2 internal deletion. This phenomenon was observed in transient transfection with a human hepatoma Huh7 cell line as well as in stable transfection with a rodent hepatoma cell line 7777. (2) A significantly increased intracellular accumulation of all three envelope proteins (large, middle, and small) was detected by both Western blot analysis and immunofluorescence microscopy. (3) The middle envelope proteins with a preS2 internal deletion were not recognized in vitro by a putative neutralizing antiserum, suggesting that these variants can evade immune recognition in vivo. To our knowledge, this is the first identification and characterization of the M deletion variant protein in HBV natural infection. (C) 2002 Elsevier Science.