鸡 TRIM45 的鉴定和表征及其作为 ALV-J 体外复制负调控因子的作用。

IF 2.5 2区 农林科学 Q1 VETERINARY SCIENCES
Avian Pathology Pub Date : 2025-04-01 Epub Date: 2024-11-08 DOI:10.1080/03079457.2024.2419039
Jiaxing Wang, Qiangzhou Wang, Yuyu Ping, Xuan Huang, Ting Yang, Yulin Bi, Guobin Chang, Shihao Chen
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引用次数: 0

摘要

禽白血病病毒 J 亚群(ALV-J)是一种感染鸡的α-反转录病毒,可导致免疫抑制和生产性能下降,给家禽业带来巨大的经济损失。ALV-J 还以其致癌特性而闻名,会诱发感染鸡的骨髓瘤和血管瘤等肿瘤。本研究旨在剖析鸡TRIM45基因的分子特征及其在ALV-J感染过程中的调控,以及其对病毒复制的影响。我们发现鸡TRIM45的RING结构域与人类和其他哺乳动物的RING结构域明显不同。TRIM45在鸡的所有组织中都有表达,其中在心脏中的表达量最高。亚细胞定位研究表明,TRIM45呈细胞质分布,在细胞内形成聚集体。我们的研究结果表明,ALV-J 感染可显著上调 TRIM45 在 DF-1 细胞中的表达。为了评估 TRIM45 在 ALV-J 复制中的功能作用,我们采用了基因沉默和过表达两种策略。令人震惊的是,TRIM45(包括缺乏 RING 结构域的突变体)的过表达被发现明显抑制了 ALV-J 的复制。与此相反,通过 siRNA 敲除 TRIM45 会导致病毒复制增强,这凸显了 TRIM45 限制 ALV-J 复制的重要性。从机理上讲,过表达 TRIM45 会诱导感染细胞凋亡,这与其 RING 结构域功能无关。总之,我们的研究表明,鸡 TRIM45 通过促进感染细胞的凋亡,在体外作为 ALV-J 复制的负调控因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification and characterization of chicken TRIM45 and its role as a negative regulator of ALV-J replication in vitro.

Avian leukosis virus subgroup J (ALV-J) is an alpharetrovirus that infects chickens, causing immunosuppression and a decrease in production performance, leading to substantial economic losses in the poultry industry. ALV-J is also well-known for its oncogenic properties, inducing tumours such as myelomas and haemangiomas in infected chickens. TRIM45 has been identified as a potential tumour suppressor; however, the relationship between TRIM45 expression and ALV-J infection remains to be elucidated. This study aimed to dissect the molecular characteristics of the chicken TRIM45 gene and its modulation during ALV-J infection, as well as its influence on viral replication. We found that the chicken TRIM45 RING domain is significantly different from that of humans and other mammals. TRIM45 is expressed in all chicken tissues, with the highest levels in the heart. Subcellular localization studies indicated a cytoplasmic distribution of TRIM45, forming aggregates within cells. Our findings demonstrate that ALV-J infection significantly upregulates TRIM45 expression in DF-1 cells. To assess the functional role of TRIM45 in ALV-J replication, we employed both gene silencing and overexpression strategies. Strikingly, the overexpression of TRIM45, including a mutant lacking the RING domain, was found to markedly suppress ALV-J replication. In contrast, TRIM45 knockdown via siRNA resulted in an enhanced viral replication, highlighting the importance of TRIM45 limiting ALV-J replication. Mechanistically, overexpression of TRIM45 induces apoptosis in infected cells, independent of its RING domain function. In conclusion, our study demonstrates that chicken TRIM45 acts as a negative regulator of ALV-J replication in vitro by promoting apoptosis in infected cells.RESEARCH HIGHLIGHTSChicken TRIM45 RING domain and protein localization significantly differ from humans.TRIM45 negatively regulates ALV-J replication in vitro.TRIM45 inhibits ALV-J replication by inducing apoptosis in infected cells.

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来源期刊
Avian Pathology
Avian Pathology 农林科学-兽医学
CiteScore
4.50
自引率
10.70%
发文量
68
审稿时长
1 months
期刊介绍: Avian Pathology is the official journal of the World Veterinary Poultry Association and, since its first publication in 1972, has been a leading international journal for poultry disease scientists. It publishes material relevant to the entire field of infectious and non-infectious diseases of poultry and other birds. Accepted manuscripts will contribute novel data of interest to an international readership and will add significantly to knowledge and understanding of diseases, old or new. Subject areas include pathology, diagnosis, detection and characterisation of pathogens, infections of possible zoonotic importance, epidemiology, innate and immune responses, vaccines, gene sequences, genetics in relation to disease and physiological and biochemical changes in response to disease. First and subsequent reports of well-recognized diseases within a country are not acceptable unless they also include substantial new information about the disease or pathogen. Manuscripts on wild or pet birds should describe disease or pathogens in a significant number of birds, recognizing/suggesting serious potential impact on that species or that the disease or pathogen is of demonstrable relevance to poultry. Manuscripts on food-borne microorganisms acquired during or after processing, and those that catalogue the occurrence or properties of microorganisms, are unlikely to be considered for publication in the absence of data linking them to avian disease.
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