Athas G B, Lobelle-Rich P, Levy L S
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
J Virol. 1995 Jun;69(6):3324-32. doi: 10.1128/JVI.69.6.3324-3332.1995.
Feline leukemia virus (FeLV) proviruses have been characterized from naturally occurring non-B-cell, non-T-cell tumors occurring in the spleens of infected cats. These proviruses exhibit a unique sequence motif in the long terminal repeat (LTR), namely, a 21-bp tandem triplication beginning 25 bp downstream of the enhancer. The repeated finding of the triplication-containing LTR in non-B-cell, non-T-cell lymphomas of the spleen suggests that the unique LTR is an essential participant in the development of tumors of this particular phenotype. The nucleotide sequence of the triplication-containing LTR most closely resembles that of FeLV subgroup C. Studies performed to measure the ability of the triplication-containing LTR to modulate gene expression indicate that the 21-bp triplication provides transcriptional enhancer function to the LTR that contains it and that it substitutes at least in part for the duplication of the enhancer. The 21-bp triplication confers a bona fide enhancer function upon LTR-directed reporter gene expression; however, the possibility of a spacer function was not eliminated. The studies demonstrate further that the triplication-containing LTR acts preferentially in a cell-type-specific manner, i.e., it is 12-fold more active in K-562 cells than is an LTR lacking the triplication. A recombinant, infectious FeLV bearing the 21-bp triplication in U3 was constructed. Cells infected with the recombinant were shown to accumulate higher levels of viral RNA transcripts and virus particles in culture supernatants than did cells infected with the parental type. The triplication-containing LTR is implicated in the induction of tumors of a particular phenotype, perhaps through transcriptional regulation of the virus and/or adjacent cellular genes, in the appropriate target cell.
猫白血病病毒（FeLV）前病毒已从受感染猫脾脏中自然发生的非B细胞、非T细胞肿瘤中得到鉴定。这些前病毒在长末端重复序列（LTR）中呈现出独特的序列基序，即在增强子下游25 bp处开始的21 bp串联重复。在脾脏的非B细胞、非T细胞淋巴瘤中反复发现含重复序列的LTR，这表明独特的LTR是这种特定表型肿瘤发生过程中的重要参与者。含重复序列的LTR的核苷酸序列与FeLV C亚群的序列最为相似。为测量含重复序列的LTR调节基因表达能力而进行的研究表明，21 bp重复序列为包含它的LTR提供转录增强子功能，并且它至少部分替代了增强子的重复。21 bp重复序列赋予LTR指导的报告基因表达真正的增强子功能；然而，间隔功能的可能性并未排除。这些研究进一步证明，含重复序列的LTR以细胞类型特异性方式优先发挥作用，即它在K - 562细胞中的活性比缺乏重复序列的LTR高12倍。构建了在U3中带有21 bp重复序列的重组感染性FeLV。与感染亲本型的细胞相比，感染重组病毒的细胞在培养上清液中积累了更高水平的病毒RNA转录本和病毒颗粒。含重复序列的LTR可能通过在适当的靶细胞中对病毒和/或相邻细胞基因进行转录调控，参与特定表型肿瘤的诱导。
