Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay.
Vet Res. 2013 Mar 18;44(1):19. doi: 10.1186/1297-9716-44-19.
It is widely accepted that the majority of cancers result from multiple cellular events leading to malignancy after a prolonged period of clinical latency, and that the immune system plays a critical role in the control of cancer progression. Bovine leukemia virus (BLV) is an oncogenic member of the Retroviridae family. Complete genomic sequences of BLV strains isolated from peripheral blood mononuclear cells (PBMC) from cattle have been previously reported. However, a detailed characterization of the complete genome of BLV strains directly isolated from bovine tumors is much needed in order to contribute to the understanding of the mechanisms of leukemogenesis induced by BLV in cattle. In this study, we performed a molecular characterization of BLV complete genomes from bovine B-cell lymphosarcoma isolates. A nucleotide substitution was found in the glucocorticoid response element (GRE) site of the 5' long terminal repeat (5'LTR) of the BLV isolates. All amino acid substitutions in Tax previously found to be related to stimulate high transcriptional activity of 5'LTR were not found in these studies. Amino acid substitutions were found in the nucleocapsid, gp51 and G4 proteins. Premature stop-codons in R3 were observed. Few mutations or amino acid substitutions may be needed to allow BLV provirus to achieve silencing. Substitutions that favor suppression of viral expression in malignant B cells might be a strategy to circumvent effective immune attack.
人们普遍认为，大多数癌症是由多个细胞事件导致的，这些事件在很长的临床潜伏期后导致恶性肿瘤，而免疫系统在控制癌症进展方面起着关键作用。牛白血病病毒（BLV）是逆转录病毒科的一种致癌成员。以前已经报道了从牛外周血单核细胞（PBMC）中分离的 BLV 株的完整基因组序列。然而，为了有助于了解 BLV 在牛中诱导白血病发生的机制，非常需要对直接从牛肿瘤中分离的 BLV 株的完整基因组进行详细表征。在这项研究中，我们对牛 B 细胞淋巴肉瘤分离株的 BLV 完整基因组进行了分子特征分析。在 BLV 分离株的 5'长末端重复（5'LTR）的糖皮质激素反应元件（GRE）位点发现了一个核苷酸取代。在这些研究中没有发现先前发现与刺激 5'LTR 高转录活性相关的 Tax 中的所有氨基酸取代。在核衣壳、gp51 和 G4 蛋白中发现了氨基酸取代。在 R3 中观察到过早的终止密码子。BLV 前病毒实现沉默可能只需要少数突变或氨基酸取代。有利于抑制恶性 B 细胞中病毒表达的取代可能是规避有效免疫攻击的一种策略。
