Latent membrane protein 1 deletion mutants accumulate in Reed-Sternberg cells of human immunodeficiency virus-related Hodgkin's lymphoma
Latent membrane protein 1 deletion mutants accumulate in Reed-Sternberg cells of human immunodeficiency virus-related Hodgkin's lymphoma
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DOI：
10.1128/jvi.79.4.2643-2649.2005
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发表时间：
2005-02-01
影响因子：
5.4
通讯作者：
Dolcetti, R
中科院分区：
文献类型：
--
作者：
Guidoboni, M;Ponzoni, M;Dolcetti, R
EB病毒（Epstein-Barr virus，EBV）编码的潜伏膜蛋白1（LMP-1）基因3'端缺失的起源和生物学意义至今仍有争议。我们在此证明，LMP-1缺失突变体与意大利患者的人类免疫缺陷病毒相关的霍奇金淋巴瘤（HIV-HL）高度相关（31例中有29例; 93.5%），这种现象并不是由于EBV毒株在该地区的特殊分布。事实上，尽管HIV-HL患者感染多种EBV变异，我们证明LMP-1缺失突变体优先在肿瘤组织内积累。对两个HIV-HL基因的3'端LMP-1末端进行亚克隆和测序，其中两个变体都存在，显示存在分子特征，提示LMP-1缺失突变体可能来自非缺失祖先。这种现象可能发生在体内肿瘤细胞内，如在单个显微解剖的Reed-Sternberg细胞中检测到两种LMP-1变体所示，并且至少可以部分解释与HIV-HL相关的LMP-1缺失的高患病率。
The origin and biological significance of deletions at the 3' end of the Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1) gene are still controversial. We herein demonstrate that LMP-1 deletion mutants are highly associated with human immunodeficiency virus-related Hodgkin's lymphoma (HIV-HL) of Italian patients (29 of 31 cases; 93.5%), a phenomenon that is not due to a peculiar distribution of EBV strains in this area. In fact, although HIV-HL patients are infected by multiple EBV variants, we demonstrate that LMP-1 deletion mutants preferentially accumulate within neoplastic tissues. Subcloning and sequencing of the 3' LMP-1 ends of two HIV-HL genes in which both variants were present showed the presence of molecular signatures suggestive of a likely derivation of the LMP-1 deletion mutant from a nondeletion ancestor. This phenomenon likely occurs within tumor cells in vivo, as shown by the detection of both LMP-1 variants in single microdissected Reed-Sternberg cells, and may at least in part explain the high prevalence of LMP-1 deletions associated with HIV-HL.