探索 TRIM25 基因表达对 COVID-19 严重程度和 SARS-CoV-2 病毒复制的影响。

IF 4.7 3区医学 Q1 INFECTIOUS DISEASES Journal of Infection and Public Health Pub Date : 2024-07-02 DOI:10.1016/j.jiph.2024.102489

Rezvan Tavakoli , Pooneh Rahimi , Abolfazl Fateh , Mojtaba Hamidi-Fard , Sana Eaybpoosh , Golnaz Bahramali , Seyed Amir Sadeghi , Delaram Doroud , Mohammadreza Aghasadeghi

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引用次数: 0

摘要

背景：有许多人类基因与病毒感染有关，在特定人群中识别这些基因可为调节宿主免疫系统反应和更好地了解病毒致病机制提供合适的治疗靶点。许多抗病毒信号通路，包括 I 型干扰素和 NF-κB 都受 TRIM 蛋白调控。因此，鉴定参与 COVID-19 感染的 TRIM 蛋白对了解该病毒的先天免疫反应具有重要作用：本研究评估了 330 名入院患者（142 名重症患者和 188 名轻症患者）和 160 名健康人血液样本中 TRIM25 基因的表达情况。通过实时定量 PCR 技术，评估并比较了该基因的表达与 COVID-19 疾病严重程度之间的关系。统计分析结果表明，与轻度感染者相比，重度感染者组中 TRIM25 的表达量明显减少。此外，还研究了TRIM25基因在HEK-293 T细胞培养中表达增加对减毒SARS-CoV-2病毒复制的影响：结果：实时 PCR、病毒核壳基因 Western 印迹和 CCID50 试验的结果表明，病毒在这些细胞中的复制减少了。研究结果表明，TRIM25 基因表达的减少与 COVID-19 患者疾病严重程度的增加有关。此外，研究结果表明，TRIM25 基因的过度表达会影响减毒的 SARS-CoV-2 的复制和 beta 干扰素的诱导：结论：TRIM25通过与病毒的直接相互作用以及在感染早期参与诱导干扰素，在控制病毒复制方面发挥着关键作用。结论：TRIM25通过与病毒的直接相互作用以及在感染早期阶段参与诱导干扰素，在控制病毒复制方面发挥着关键作用。

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Exploring the impression of TRIM25 gene expression on COVID-19 severity and SARS-CoV-2 viral replication

Background

There are numerous human genes associated with viral infections, and their identification in specific populations can provide suitable therapeutic targets for modulating the host immune system response and better understanding the viral pathogenic mechanisms. Many antiviral signaling pathways, including Type I interferon and NF-κB, are regulated by TRIM proteins. Therefore, the identification of TRIM proteins involved in COVID-19 infection can play a significant role in understanding the innate immune response to this virus.

Methods

In this study, the expression of TRIM25 gene was evaluated in a blood sample of 330 patients admitted to the hospital (142 patients with severe disease and 188 patients with mild disease) as well as in 160 healthy individuals. The relationship between its expression and the severity of COVID-19 disease was assessed and compared among the study groups by quantitative Real-time PCR technique. The statistical analysis of the results demonstrated a significant reduction in the expression of TRIM25 in the group of patients with severe infection compared to those with mild infection. Furthermore, the impact of increased expression of TRIM25 gene in HEK-293 T cell culture was investigated on the replication of attenuated SARS-CoV-2 virus.

Results

The results of Real-time PCR, Western blot for the viral nucleocapsid gene of virus, and CCID₅₀ test indicated a decrease in virus replication in these cells. The findings of this research indicated that the reduced expression of the TRIM25 gene was associated with increased disease severity of COVID-19 in individuals. Additionally, the results suggested the overexpression of TRIM25 gene can impress the replication of attenuated SARS-CoV-2 and the induction of beta-interferon.

Conclusion

TRIM25 plays a critical role in controlling viral replication through its direct interaction with the virus and its involvement in inducing interferon during the early stages of infection. This makes TRIM25 a promising target for potential therapeutic interventions.

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来源期刊

Journal of Infection and Public Health PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH -INFECTIOUS DISEASES

CiteScore

13.10

自引率

1.50%

发文量

203

审稿时长

96 days

期刊介绍： The Journal of Infection and Public Health, first official journal of the Saudi Arabian Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences and the Saudi Association for Public Health, aims to be the foremost scientific, peer-reviewed journal encompassing infection prevention and control, microbiology, infectious diseases, public health and the application of healthcare epidemiology to the evaluation of health outcomes. The point of view of the journal is that infection and public health are closely intertwined and that advances in one area will have positive consequences on the other. The journal will be useful to all health professionals who are partners in the management of patients with communicable diseases, keeping them up to date. The journal is proud to have an international and diverse editorial board that will assist and facilitate the publication of articles that reflect a global view on infection control and public health, as well as emphasizing our focus on supporting the needs of public health practitioners. It is our aim to improve healthcare by reducing risk of infection and related adverse outcomes by critical review, selection, and dissemination of new and relevant information in the field of infection control, public health and infectious diseases in all healthcare settings and the community.