Department of Animal Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Department of Animal Science, Ferdowsi University of Mashhad, Mashhad, Iran; Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
Microb Pathog. 2020 Feb;139:103845. doi: 10.1016/j.micpath.2019.103845. Epub 2019 Nov 4.
Human T-cell lymphotropic virus (HTLV-1) and bovine leukemia virus (BLV) are oncogenic deltaretroviruses, which are the cause of adult T cell leukemia/lymphoma (ATLL) and enzootic bovine leukosis (EBL), respectively. In this study, to evaluate the virus-host interactions in the manifestation of the associated malignancy, four pooled RNA samples of each host (three RNAs in each sample) were applied to RNA-seq. Differential expression analyses were conducted separately between ATLL and EBL groups, in comparison with the healthy group, to identify functional Gene Ontology (GO) terms and hub genes, using DAVID database and MCODE plugin in Cytoscape software, respectively. A broad range of effective genes, involved in the ATLL and EBL, was up- and downregulated. In the virus side, in both malignancy, Tax was expressed very low, but the HTLV-1-HBZ and BVL-As2 transcripts were highly expressed. Some upregulated hub genes, IL2, TOP2A, MKI67, TP73, MYC, and downregulated FOS gene family (FOS, FOSB, and FOSL2), are similarly activated in both human and bovine hosts, in related cell cycle and growth factors. Taken together, it seems that in preventing the infections and cell transformations, Tax must be targeted as a viral factor, and shared peptide in virological and immunological synapses as host factors. Therefore, in the malignant stages, HBZ and As2 transcripts along with growth factors, particularly IL-2R-γ and T-bet or TOP2A, and MKI67 should be targeted in both hosts. Additional studies at the protein level are necessary to elucidate the more useful targets for the therapy of these life-threatening diseases.
人类 T 细胞白血病病毒（HTLV-1）和牛白血病病毒（BLV）是致瘤的δ逆转录病毒，分别是成人 T 细胞白血病/淋巴瘤（ATLL）和牛白血病（EBL）的病因。在这项研究中，为了评估病毒-宿主相互作用在相关恶性肿瘤中的表现，将每个宿主的四个 RNA 样本（每个样本中包含 3 个 RNA）应用于 RNA-seq。通过 DAVID 数据库和 Cytoscape 软件中的 MCODE 插件，分别在 ATLL 和 EBL 组与健康组之间进行差异表达分析，以识别功能基因本体论（GO）术语和枢纽基因。广泛的有效基因，涉及 ATLL 和 EBL，被上调和下调。在病毒方面，在两种恶性肿瘤中，Tax 的表达非常低，但 HTLV-1-HBZ 和 BVL-As2 转录本高度表达。一些上调的枢纽基因，如 IL2、TOP2A、MKI67、TP73、MYC 和下调的 FOS 基因家族（FOS、FOSB 和 FOSL2），在人类和牛宿主中同样被激活，与细胞周期和生长因子有关。总之，似乎在预防感染和细胞转化中，Tax 必须作为病毒因子，而共享的肽在病毒学和免疫突触中作为宿主因子被靶向。因此，在恶性阶段，HBZ 和 As2 转录本以及生长因子，特别是 IL-2R-γ 和 T-bet 或 TOP2A 和 MKI67，应该在两个宿主中被靶向。需要在蛋白质水平上进行更多的研究，以阐明这些危及生命的疾病治疗的更有用的靶点。
