EPSTEIN-BARR VIRUS NUCLEAR PROTEIN-2 IS A KEY DETERMINANT OF LYMPHOCYTE-TRANSFORMATION
EPSTEIN-BARR VIRUS NUCLEAR PROTEIN-2 IS A KEY DETERMINANT OF LYMPHOCYTE-TRANSFORMATION
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DOI：
10.1073/pnas.86.23.9558
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发表时间：
1989-12-01
影响因子：
11.1
通讯作者：
KIEFF, E
中科院分区：
文献类型：
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作者：
COHEN, JI;WANG, F;KIEFF, E
爱泼斯坦-巴尔病毒(EBV)能有效地将B淋巴细胞转化为永续增殖。EBV实验室毒株P3HR-1不具备转化能力，缺乏包含EBV核抗原2(EBNA-2)基因和EBNA领导蛋白(EBNA-LP)部分基因的DNA片段。这两个基因在转化后的B淋巴细胞中表达。将含有P3HR-1缺失DNA的粘粒导入P3HR-1感染细胞，获得具有转化能力的重组EBV。EBNA-2基因中间105个核苷酸的缺失对转化没有明显影响。两个较大的EBNA-2缺失取消了转化，但不影响EBNA-2的核定位。两个自然产生的EBV变异体(EBV类型1和2)在生长转化表型和EBNA-LP、EBNA-2和EBNA-3A、-3B和-3C基因上存在很大差异。携带EBV-1 EBNA-2的重组P3HR-1在体外具有许多EBV-1的生长转化作用；重组P3HR-1除EBV-2 EBNA-2外，与EBV-2同源，具有许多EBV-2的生长转化作用，包括转化子出现缓慢，周围活细胞很少的紧密丛生生长，以及对新鲜培养基稀释的早期敏感性。因此，EBNA-2是EBV诱导的淋巴细胞生长转化过程中必不可少的分子，也是EBV-1和EBV-2在淋巴细胞生长转化过程中差异的主要决定因素。
Epstein-Barr virus (EBV) efficiently transforms B lymphocytes to perpetual proliferation. The EBV laboratory strain P3HR-1 is transformation-incompetent and lacks a DNA segment that includes the EBV nuclear antigen 2 (EBNA-2) gene and a portion of the EBNA leader protein (EBNA-LP) gene. These two genes are expressed in transformed B lymphocytes. Recombinant transformation-competent EBVs were produced by transfecting P3HR-1-infected cells with a cosmid containing the DNA deleted in P3HR-1. Deletion of 105 nucleotides from the middle of the EBNA-2 gene had no discernible effect on transformation. Two larger EBNA-2 deletions abolished transformation but did not affect EBNA-2 nuclear localization. Two naturally occurring EBV variants (EBV types 1 and 2) differ extensively in their growth-transformation phenotype and in their EBNA-LP, EBNA-2, and EBNA-3A, -3B, and -3C genes. Recombinant P3HR-1 carrying EBV-1 EBNA-2 has many of the EBV-1 in vitro growth-transforming effects; recombinant P3HR-1, isogenic except for EBV-2 EBNA-2, has many of the EBV-2 growth-transforming effects including slow emergence of transformants, growth in tight clumps with few surrounding viable cells, and early sensitivity to dilution with fresh medium. Thus, EBNA-2 is an essential molecule in lymphocyte growth transformation by EBV and a major determinant of the differences between EBV-1 and EBV-2 in lymphocyte growth transformation.