Letafati Arash, Bahavar Atefeh, Tabarraei Alijan, Norouzi Mehdi, Amiri Abdollah, Mozhgani Sayed-Hamidreza
Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran.
Infect Agent Cancer. 2024 May 11;19(1):23. doi: 10.1186/s13027-024-00584-5.
Human T-cell Lymphotropic virus type 1 (HTLV-1) belongs to retroviridae which is connected to two major diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell leukemia/lymphoma (ATLL). This study aims to investigate the mRNA expressions of key proteins correlated to T-cell activation in asymptomatic carriers (ACs) HTLV-1 infected patients, shedding light on early molecular events and T-cell activation following HTLV-1 infection.
The study involved 40 participants, including 20 ACs and 20 healthy subjects. Blood samples were collected, ELISA assessment for screening and confirmation with PCR for Trans-activating transcriptional regulatory protein (Tax) and HTLV-1 basic leucine zipper factor (HBZ) of the HTLV-1 were done. mRNA expressions of C-terminal Src kinase (CSK), Glycogen Synthase Kinase-3 Beta (GSK3β), Mitogen-Activated Protein Kinase 14 (MAP3K14 or NIK), Phospholipase C Gamma-1 (PLCG1), Protein Tyrosine Phosphatase non-Receptor Type 6 (PTPN6) and Mitogen-Activated Protein Kinase Kinase Kinase-7 (SLP-76) and Mitogen-Activated Protein Kinase14 (MAP3K7 or TAK1) were assayed using RT-qPCR. Statistical analyses were performed using PRISM and SPSS software.
While there were no significant upregulation in CSK and PTPN6 in ACs compared to healthy individuals, expression levels of GSK3β, MAP3K14, PLCG1, SLP-76, and TAK1 were significantly higher in ACs compared to healthy subjects which directly contributes to T-cell activation in the HTLV-1 ACs.
HTLV-1 infection induces differential mRNA expressions in key proteins associated with T-cell activation. mRNAs related to T-cell activation showed significant upregulation compared to PTPN6 and CSK which contributed to T-cell regulation. Understanding these early molecular events in ACs may provide potential markers for disease progression and identify therapeutic targets for controlling viral replication and mitigating associated diseases. The study contributes novel insights to the limited literature on T-cell activation and HTLV-1 pathogenesis.
人类嗜T细胞病毒1型（HTLV-1）属于逆转录病毒科，与两种主要疾病相关，包括HTLV-1相关脊髓病/热带痉挛性截瘫（HAM/TSP）和成人T细胞白血病/淋巴瘤（ATLL）。本研究旨在调查HTLV-1感染的无症状携带者（ACs）中与T细胞活化相关的关键蛋白的mRNA表达，以揭示HTLV-1感染后的早期分子事件和T细胞活化情况。
该研究纳入了40名参与者，包括20名ACs和20名健康受试者。采集血样后，进行ELISA检测以筛选，并通过PCR检测HTLV-1的反式激活转录调节蛋白（Tax）和HTLV-1碱性亮氨酸拉链因子（HBZ）以进行确认。使用RT-qPCR检测C末端Src激酶（CSK）、糖原合酶激酶-3β（GSK3β）、丝裂原活化蛋白激酶14（MAP3K14或NIK）、磷脂酶Cγ-1（PLCG1）、蛋白酪氨酸磷酸酶非受体型6（PTPN6）、丝裂原活化蛋白激酶激酶激酶-7（SLP-76）和丝裂原活化蛋白激酶14（MAP3K7或TAK1）的mRNA表达。使用PRISM和SPSS软件进行统计分析。
与健康个体相比，ACs中CSK和PTPN6没有明显上调，但与健康受试者相比，ACs中GSK3β、MAP3K14、PLCG1、SLP-76和TAK1的表达水平显著更高，这直接导致了HTLV-1 ACs中的T细胞活化。
HTLV-1感染诱导了与T细胞活化相关的关键蛋白的差异mRNA表达。与T细胞活化相关的mRNA与有助于T细胞调节的PTPN6和CSK相比，显示出显著上调。了解ACs中的这些早期分子事件可能为疾病进展提供潜在标志物，并确定控制病毒复制和减轻相关疾病的治疗靶点。该研究为关于T细胞活化和HTLV-1发病机制的有限文献提供了新的见解。
