Human T-cell Leukemia Virus type-1 (HTLV-1) is a retrovirus that causes two diseases including Adult T-cell Leukemia/Lymphoma (ATLL cancer) and HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP, a neurodegenerative disease) after a long latency period as an asymptomatic carrier (AC). There are no obvious explanations about how each of the mentioned diseases develops in the AC carriers. Finding the discriminative molecular factors and pathways may clarify the destiny of the infection. To shed light on the involved molecular players and activated pathways in each state, differentially co-expressed modules (DiffCoEx) algorithm was employed to identify the highly correlated genes which were co-expressed differently between normal and ACs, ACs and ATLL, as well as ACs and HAM/TSP samples. Through differential pathway analysis, the dysregulated pathways and the specific disease-genes-pathways were figured out. Moreover, the common genes between the member of DiffCoEx and differentially expressed genes were found and the specific genes in ATLL and HAM/TSP were introduced as possible biomarkers. The dysregulated genes in the ATLL were mostly enriched in immune and cancer-related pathways while the ones in the HAM/TSP were enriched in immune, inflammation, and neurological pathways. The differential pathway analysis clarified the differences between the gene players in the common activated pathways. Eventually, the final analysis revealed the involvement of specific dysregulated genes including KIRREL2, RAB36, and KANK1 in HAM/TSP as well as LTB4R2, HCN4, FZD9, GRIK5, CREB3L4, TACR2, FRMD1, LHB, FGF3, TEAD3, GRIN2D, GNRH2, PRLH, GPR156, and CRHR2 in ATLL. The identified potential prognostic biomarkers and therapeutic targets are proposed as the most important platers in developing ATLL or HAM/TSP. Moreover, the proposed signaling network clarifies the differences between the functional players in the activated pathways in ACs, ATLL, and HAM/TSP.

中文翻译：

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通过系统病毒学研究解码与 HTLV-1 感染后 ATLL 或 HAM/TSP 进展有关的发病机制

人类 T 细胞白血病病毒 1 型 (HTLV-1) 是一种逆转录病毒，可导致两种疾病，包括成人 T 细胞白血病/淋巴瘤（ATLL 癌）和 HTLV-1 相关脊髓病/热带痉挛性截瘫（HAM/TSP，一种神经退行性疾病）疾病）作为无症状携带者（AC）经过长时间的潜伏期后。关于上述每种疾病如何在 AC 携带者中发展，没有明显的解释。寻找可区分的分子因素和途径可能会阐明感染的命运。为了阐明每个状态中涉及的分子参与者和激活通路，采用差异共表达模块 (DiffCoEx) 算法来识别在正常和 AC、AC 和 ATLL 之间以不同方式共表达的高度相关基因，以及AC 和 HAM/TSP 样本。通过差异通路分析，找出了失调的途径和特定的疾病基因途径。此外，发现了DiffCoEx成员与差异表达基因之间的共同基因，并引入了ATLL和HAM/TSP中的特定基因作为可能的生物标志物。ATLL 中失调的基因主要富集于免疫和癌症相关通路，而 HAM/TSP 中的基因富集于免疫、炎症和神经通路。差异通路分析阐明了常见激活通路中基因参与者之间的差异。最终，最终分析揭示了特定失调基因的参与，包括 KIRREL2、RAB36 和 KANK1 在 HAM/TSP 以及 LTB4R2、HCN4、FZD9、GRIK5、CREB3L4、TACR2、FRMD1、LHB、FGF3、TEAD3、GRIN2D、GNRH2、 ATLL 中的 PRLH、GPR156 和 CRHR2。已确定的潜在预后生物标志物和治疗靶点被认为是开发 ATLL 或 HAM/TSP 中最重要的标记物。此外，所提出的信号网络阐明了 AC、ATLL 和 HAM/TSP 中激活通路中功能参与者之间的差异。