ATTENUATION OF BOVINE LEUKEMIA-VIRUS BY DELETION OF R3 AND G4 OPEN READING FRAMES
ATTENUATION OF BOVINE LEUKEMIA-VIRUS BY DELETION OF R3 AND G4 OPEN READING FRAMES
复制标题
DOI：
10.1073/pnas.91.24.11532
复制
发表时间：
1994-11-22
影响因子：
11.1
通讯作者：
KETTMANN, R
中科院分区：
文献类型：
--
作者：
WILLEMS, L;KERKHOFS, P;KETTMANN, R
除了经典逆转录病毒基因（gag、pol和env）外，复杂的癌病毒还含有一个位于包膜序列和3'长末端重复序列之间的区域(X)。X区包含tar和rer两个基因，其蛋白产物参与病毒表达的转录和转录后调控。除了这些激活因子外，牛白血病病毒（BLV）和人t细胞白血病病毒（HTLV）还含有其他开放阅读框（BLV为R3和G4； HTLV为p30、p13和p12）。作为htlv诱导白血病的病毒/动物模型，BLV病毒可以皮下注射到绵羊体内，诱导b淋巴细胞转化。DNA聚合酶链反应、RNA印迹、结构蛋白ELISA和免疫荧光分析表明，从一种传染性和致瘤性BLV原病毒中删除R3和G4序列会极大地损害病毒的体内繁殖。我们的研究结果表明，在体内持续感染过程中，需要替代的开放阅读框来维持高病毒载量。因此，R3和G4是抗病毒药物开发的候选药物。此外，在这些序列中有缺失的病毒应作为减毒活疫苗进行试验。
Complex oncoviruses contain, in addition to the classical retroviral genes (gag, pol, and env), a region (X) located between the envelope sequences and the 3' long terminal repeat. The X region contains two genes, tar and rer, whose protein products are involved in transcriptional and posttranscriptional regulation of viral expression. In addition to these activators, the bovine leukemia virus (BLV) and the human T-cell leukemia virus (HTLV) contain alternative open reading frames (R3 and G4 for BLV; p30, p13, and p12 for HTLV). As a virus/animal model for HTLV-induced leukemogenesis, BLV provirus can be injected intradermally into sheep, where it induced B-lymphocyte transformation. Deletion of the R3 and G4 sequences from an infectious and tumorigenic BLV provirus greatly impaired the in vivo propagation of the viruses as demonstrated by DNA polymerase chain reaction, RNA blots, structural-protein ELISA, and immunofluorescence analysis. Our results show that the alternative open reading frames are required for maintaining high virus loads during the course of persistent infection in vivo. Thus, R3 and G4 are candidates for antiviral drug development. Furthermore, viruses with a deletion in these sequences should be tested as live attenuated vaccines.