Background

Human T-cell lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) are oncogenic viruses that induce adult T cell leukemia/lymphoma (ATLL) and enzootic bovine leukosis (EBL), respectively. HTLV-1 principally infects CD4⁺ T cells comprising regulatory T cells (Tregs), T helper 1 (Th1), and T helper 2 (Th2), while BLV infects B lymphocytes. Both viruses may impel cell proliferation and malignancy.

Methods

To survey the transcriptomic variations due to HTLV-1 and BLV infection and further hematologic malignancies, differential expression genes (DEGs) were explored between leukemia and normal samples using the DESeq2 package. Gene set enrichment analyses (GSEA) were then performed to identify significant gene sets using the FGSEA package. Afterward, the protein-protein interaction (PPI) networks were reconstructed using the STRING online database. Eventually, the hub significant genes and modules were determined through network analysis and MCODE algorithm, respectively.

Results

Our results uncloaked that four common functional gene sets including mitotic-spindle, G2M-checkpoint, E2F-targets, and MYC-targets-V1 are involved in the human and ovine hosts. Furthermore, twelve up-regulated hub genes including BIRC5, CCNA2, CCNB2, BUB1, DLGAP5, TOP2A, PBK, ASPM, UBE2C, CEP55, KIF20A, and NUSAP1 were identified which were similarly activated in both human and ovine hosts. They mostly participate in pathways including cell cycle, cell division, DNA damage responses, growth factors production, and p53 signaling pathway. The dysregulated hub genes and pathways seem to be involved in the development and progression of the infected cells toward malignancy.

Conclusion

There is common gene groups between HTLV-1 and BLV infections that promote viral malignancy through enhancing cell proliferation and overall survival of cancer cells. The dysregulated genes and pathways may be the efficient candidates for the therapy of the mentioned life-threatening diseases.

中文翻译：

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通过综合系统生物学分析鉴定与 HTLV-1 和 BLV 发病机制有关的联合基因参与者

背景

人类 T 细胞嗜淋巴细胞病毒 1 型 (HTLV-1) 和牛白血病病毒 (BLV) 是致癌病毒，分别诱导成人 T 细胞白血病/淋巴瘤 (ATLL) 和地方性牛白血病 (EBL)。HTLV-1 主要感染包括调节性 T 细胞 (Tregs)、T 辅助细胞 1 (Th1) 和 T 辅助细胞 2 (Th2)的 CD4 ^{+ T 细胞，而 BLV 感染 B 淋巴细胞。}这两种病毒都可能促使细胞增殖和恶性。

方法

为了调查由于 HTLV-1 和 BLV 感染以及进一步的血液系统恶性肿瘤引起的转录组变异，使用 DESeq2 包在白血病和正常样本之间探索了差异表达基因 (DEG)。然后使用 FGSEA 包进行基因集富集分析 (GSEA) 以识别重要的基因集。之后，使用 STRING 在线数据库重建蛋白质-蛋白质相互作用 (PPI) 网络。最终，通过网络分析和MCODE算法分别确定了枢纽重要基因和模块。

结果

我们的研究结果揭示了四种常见的功能基因组，包括有丝分裂纺锤体、G2M-检查点、E2F-靶标和 MYC-靶标-V1，参与人类和绵羊宿主。此外，鉴定了 12 个上调的中枢基因，包括BIRC5、CCNA2、CCNB2、BUB1、DLGAP5、TOP2A、PBK、ASPM、UBE2C、CEP55、KIF20A和NUSAP1，它们在人和绵羊宿主中都被类似地激活。它们主要参与包括细胞周期、细胞分裂、DNA损伤反应、生长因子产生和p53信号通路在内的途径。失调的中枢基因和通路似乎与受感染细胞向恶性肿瘤的发展和进展有关。

结论

HTLV-1 和 BLV 感染之间存在共同的基因组，它们通过增强细胞增殖和癌细胞的总体存活率来促进病毒恶性。失调的基因和途径可能是治疗上述威胁生命的疾病的有效候选者。