Hatanaka M, Kobayashi N
Princess Takamatsu Symp. 1984;15:205-17.
Gallo and his coworkers isolated a retrovirus (HTLV) from human cells derived from T-cell leukemia and lymphoma. Hinuma and his coworkers isolated independently a similar virus from a cell line derived from adult T-cell leukemia (ATL) patient. The occurrence of ATL correlates with the formation of antibody to ATL associated antigens or ATLA. To understand the etiological relationship between ATL and HTLV, we analyzed the antigens termed ATLA and found that they are polypeptides encoded by HTLV genome. We further studied the genome of HTLV and its gene expression in cells as well as in a cell-free translation system. We focused on a defective type HTLV produced from a cell line MT-2 that transforms normal lymphocytes most efficiently. The 24S defective gene of HTLV consists of a fused gene of gag-pXs and is amplified at the proviral state. The in vitro translation experiments revealed that the 24S defective gene of HTLV directs the synthesis of p28 of ATLA. By the sequence analysis of the amplified gag-pXs fused genes, we found that a carboxy terminal portion of p28 is translated from a pX-0 region. We further investigated a function of the gag-pX-0 fusion protein, p28. The p28 has an associated protein kinase activity that requires manganese instead of magnesium and phosphorylates the serine residue specifically. Another defective HTLV with a genomic 32S RNA was analyzed. The 32S defective genomic RNA forms a subgenomic 20S RNA in cells. The 20S mRNA is a transcript of an env-pXs fused genome and directs the synthesis of a fused glycoprotein, gp68 of ATLA. The sequence analysis of a cloned cDNA derived from the subgenomic 20S mRNA revealed that a coding frame of the entire pX-IV region is translated. In fact, an antibody against synthetic polypeptides of the pX-IV, immunoprecipitated the gp68. These results demonstrate at the first time that the pX-0 and pX-IV of HTLV genome are expressed in human cells. The biological activities of the fused pXs proteins are also discussed. Human T-cell leukemia virus type I (HTLV-I), a family of human retrovirus and the predicted causative agent of human adult T-cell leukemia/lymphoma (ATL) consists of the gag, pol, env, and pX regions (1).(ABSTRACT TRUNCATED AT 400 WORDS)
加洛及其同事从源自T细胞白血病和淋巴瘤的人类细胞中分离出一种逆转录病毒（HTLV）。日沼及其同事则独立地从一名成人T细胞白血病（ATL）患者的细胞系中分离出一种类似病毒。ATL的发生与针对ATL相关抗原或ATLA的抗体形成有关。为了了解ATL与HTLV之间的病因关系，我们分析了被称为ATLA的抗原，发现它们是由HTLV基因组编码的多肽。我们进一步研究了HTLV的基因组及其在细胞以及无细胞翻译系统中的基因表达。我们重点研究了从最有效地转化正常淋巴细胞的MT - 2细胞系产生的一种缺陷型HTLV。HTLV的24S缺陷基因由gag - pXs融合基因组成，并在原病毒状态下扩增。体外翻译实验表明，HTLV的24S缺陷基因指导ATLA的p28合成。通过对扩增的gag - pXs融合基因的序列分析，我们发现p28的羧基末端部分是从pX - 0区域翻译而来。我们进一步研究了gag - pX - 0融合蛋白p28的功能。p28具有一种相关的蛋白激酶活性，该活性需要锰而非镁，并且特异性地磷酸化丝氨酸残基。我们还分析了另一种具有基因组32S RNA的缺陷型HTLV。32S缺陷型基因组RNA在细胞中形成亚基因组20S RNA。20S mRNA是env - pXs融合基因组的转录本，指导融合糖蛋白ATLA的gp68合成。对源自亚基因组20S mRNA的克隆cDNA的序列分析表明，整个pX - IV区域的编码框被翻译。事实上，针对pX - IV合成多肽的抗体免疫沉淀了gp68。这些结果首次证明HTLV基因组的pX - 0和pX - IV在人类细胞中表达。我们还讨论了融合pXs蛋白的生物学活性。人类I型T细胞白血病病毒（HTLV - I）是人类逆转录病毒家族，也是人类成人T细胞白血病/淋巴瘤（ATL）的推测病原体，它由gag、pol、env和pX区域组成（1）。（摘要截选至400字）
