人类 T 细胞淋巴细胞病毒 1 型（HTLV-1）对 T 细胞的控制：研究激活的病毒织锦。

IF 3.1 2区医学 Q3 IMMUNOLOGY

Infectious Agents and Cancer Pub Date : 2024-05-11 DOI:10.1186/s13027-024-00584-5

Arash Letafati, Atefeh Bahavar, Alijan Tabarraei, Mehdi Norouzi, Abdollah Amiri, Sayed-Hamidreza Mozhgani

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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. 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引用次数: 0

摘要

简介人类T细胞淋巴细胞病毒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相关骨髓病/热带痉挛性截瘫（HAM/TSP）和成人T细胞白血病/淋巴瘤（ATLL）。本研究旨在调查无症状携带者（ACs）HTLV-1感染者中与T细胞活化相关的关键蛋白的mRNA表达，揭示HTLV-1感染后的早期分子事件和T细胞活化：研究涉及 40 名参与者，包括 20 名无症状携带者和 20 名健康受试者。采集血样，用酶联免疫吸附试验（ELISA）进行筛查，并用聚合酶链式反应（PCR）确认 HTLV-1 的转录激活调控蛋白（Tax）和 HTLV-1 基本亮氨酸拉链因子（HBZ）。C-terminal Src kinase (CSK), Glycogen Synthase Kinase-3 Beta (GSK3β), Mitogen-Activated Protein Kinase 14 (MAP3K14 or NIK), Phospholipase C Gamma-1 (PLCG1)、使用 RT-qPCR 检测了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-7（SLP-76）和丝裂原活化蛋白激酶 14（MAP3K7 或 TAK1）。使用 PRISM 和 SPSS 软件进行统计分析：结果：与健康人相比，ACs 中 CSK 和 PTPN6 的表达没有明显上调，但与健康人相比，ACs 中 GSK3β、MAP3K14、PLCG1、SLP-76 和 TAK1 的表达水平明显升高，这直接导致了 HTLV-1 ACs 中 T 细胞的活化：与T细胞活化相关的mRNA与PTPN6和CSK相比有明显的上调，而PTPN6和CSK有助于T细胞的调节。了解 AC 中的这些早期分子事件可为疾病进展提供潜在标记，并确定控制病毒复制和减轻相关疾病的治疗目标。这项研究为有关 T 细胞活化和 HTLV-1 发病机制的有限文献提供了新的见解。

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Human T-cell lymphotropic virus type 1 (HTLV-1) grip on T-cells: investigating the viral tapestry of activation.

Introduction: 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.

Material and methods: 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.

Results: 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.

Conclusion: 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.

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来源期刊

Infectious Agents and Cancer ONCOLOGY-IMMUNOLOGY

CiteScore

5.80

自引率

2.70%

发文量

期刊介绍： Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer. The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular: • HPV and anogenital cancers, as well as head and neck cancers; • EBV and Burkitt lymphoma; • HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases; • HHV8 and Kaposi sarcoma; • HTLV and leukemia; • Cancers in Low- and Middle-income countries. The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries. Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.