Ratner L, Fisher A, Jagodzinski L L, Mitsuya H, Liou R S, Gallo R C, Wong-Staal F
AIDS Res Hum Retroviruses. 1987 Spring;3(1):57-69. doi: 10.1089/aid.1987.3.57.
To examine the mechanism of lymphocytotoxicity induced by human T-lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV), an in vitro model has been developed. Introduction of an HTLV-III/LAV proviral clone, HXB2, into normal lymphocytes results in the production of virions and cell death. The complete nucleotide sequence of the proviral form of HXB2 has now been determined. Its structure is quite similar to that previously determined for HTLV-III/LAV clones whose biological capacities had not previously been demonstrated. The biological function of two additional clones of HTLV-III/LAV, BH10 and HXB3, are reported. Clone BH10 which lacks the 5' long terminal repeat sequences (LTR) and a portion of the 3' LTR is reconstituted by substituting the corresponding sequences of HXB2 and is shown to be capable of generating infectious cytopathic virions. Clone HXB3, which has been partially sequenced, is also found to be capable of producing lymphocytopathic virus. Clone HXB3 differs from HXB2 in its lack of a termination codon in 3' orf, demonstrating that 3' orf plays no major role in virus replication or cytopathic activity. These data provide the necessary background to allow the identification of viral determinants of replication, cytopathic activity, and antigenicity using these functional proviral clones.
为了研究人类嗜T淋巴细胞病毒III型/淋巴结病相关病毒（HTLV-III/LAV）诱导淋巴细胞毒性的机制，已建立了一种体外模型。将HTLV-III/LAV前病毒克隆HXB2导入正常淋巴细胞会导致病毒粒子的产生和细胞死亡。现在已经确定了HXB2前病毒形式的完整核苷酸序列。其结构与先前确定的HTLV-III/LAV克隆非常相似，这些克隆的生物学能力此前尚未得到证实。报告了另外两个HTLV-III/LAV克隆BH10和HXB3的生物学功能。缺乏5'长末端重复序列（LTR）和部分3'LTR的克隆BH10通过替换HXB2的相应序列进行重建，并显示能够产生具有感染性的细胞病变病毒粒子。已进行部分测序的克隆HXB3也被发现能够产生淋巴细胞病变病毒。克隆HXB3与HXB2的不同之处在于其3'orf中缺乏终止密码子，这表明3'orf在病毒复制或细胞病变活性中不起主要作用。这些数据提供了必要的背景信息，以便利用这些功能性前病毒克隆鉴定病毒复制、细胞病变活性和抗原性的决定因素。
