EPSTEIN-BARR-VIRUS LATENT MEMBRANE PROTEIN-1 IS ESSENTIAL FOR B-LYMPHOCYTE GROWTH TRANSFORMATION

EPSTEIN-BARR-VIRUS LATENT MEMBRANE PROTEIN-1 IS ESSENTIAL FOR B-LYMPHOCYTE GROWTH TRANSFORMATION
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DOI:
10.1073/pnas.90.19.9150
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发表时间:
1993-10-01
影响因子:
11.1
通讯作者:
KIEFF, E
KIEFF, E
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KAYE, KM;IZUMI, KM;KIEFF, E

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在eb病毒(EBV)重组体中,编码潜伏感染膜蛋白1 (LMP1)的基因通过将无义连接子插入密码子9或密码子84后或插入186 bp 3'的内含子中而发生特异性突变。LMP1内含子突变的EBV重组体在原代B淋巴细胞中表达和生长转化为野生型。相比之下,在LMP1开放阅读框中突变的EBV重组体表达n端截断的交叉反应蛋白,只有当野生型LMP1由共同感染的转化缺陷EBV P3HR-1提供时,才能启动或维持原代b淋巴细胞转化。这些数据表明,LMP1对ebv介导的原代B淋巴细胞转化至关重要,前43个氨基酸对LMP1的功能至关重要,密码子44启动的LMP1对转化没有显性的负面影响。
The gene encoding latent-infection membrane protein 1 (LMP1) was specifically mutated in Epstein-Barr virus (EBV) recombinants by inserting a nonsense linker after codon 9 or codon 84 or into an intron 186 bp 3' to the latter insertion site. EBV recombinants with the LMP1 intron mutation were wild type for LMP1 expression and for growth transformation of primary B lymphocytes. In contrast, EBV recombinants with the mutations in the LMP1 open reading frame expressed N-terminally truncated crossreactive proteins and could initiate or maintain primary B-lymphocyte transformation only when wild-type LMP1 was provided in trans by a coinfecting, transformation-defective EBV, P3HR-1. These data indicate that LMP1 is essential for EBV-mediated transformation of primary B lymphocytes, that the first 43 amino acids are critical for LMP1's function, and that codon 44-initiated LMP1 does not have a dominant negative effect on transformation.