Proteomic profiling identifies nucleolin as a U3-interacting protein that inhibits avian leukosis virus replication

IF 2.8 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology Pub Date : 2026-05-01 Epub Date: 2026-02-27 DOI:10.1016/j.vetmic.2026.110957

Ziqi An , Qinghua Huang , Yawen Liu , Peipei Wang , Ning Cui , Chuantian Xu , Shuai Su

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引用次数: 0

Abstract

The long terminal repeat (LTR) of the avian retroviruses has been extensively characterized as a model of a strong transcription regulatory unit. U3 gene of LTR contains many cis-acting elements and trans-acting factors that bind to a variety of host transcription factors to form a complex network regulating high levels of transcription of viral and host genes. However, the host proteins that bind to the U3 gene and their complex mechanisms are largely unknown. In the present study, coupling surface-plasmon resonance and mass spectrometry were performed to identify proteins binding to the U3 gene of avian leukosis virus (ALV). A total of 181 U3-binding proteins with score > 20 were identified. Six of the proteins with score > 120 were successfully knockdown using siRNA transfection and the transcription of ALV gp85 mRNA was significantly increased when the nucleolin (NCL) was down regulated. The effect of NCL interference was optimized by combining siRNAs and we found that down regulation of NCL significantly increased the transcription activity of LTR, the enhancer ability of U3, and furthermore enhanced the expression of viral protein. On the contrary, over expression of NCL significantly decreased the transcription activity of LTR, the enhancer ability of U3, and the expression level of viral protein. These data demonstrate that NCL is critical for inhibition ALV replication and laid a molecular basis for development of efficient strategies against retroviruses from a new perspective.

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蛋白质组学分析鉴定核蛋白是一种抑制禽白血病病毒复制的u3相互作用蛋白。

禽类逆转录病毒的长末端重复序列（long terminal repeat， LTR）被广泛认为是一种强大的转录调控单元。LTR的U3基因含有许多顺式作用元件和反式作用因子，它们与多种宿主转录因子结合，形成一个复杂的网络，调控病毒和宿主基因的高水平转录。然而，与U3基因结合的宿主蛋白及其复杂机制在很大程度上是未知的。本研究采用表面等离子体共振和质谱联用技术对禽白血病病毒（ALV） U3基因结合蛋白进行了鉴定。共鉴定出181个得分为> 20的u3结合蛋白。siRNA转染成功敲低了6个评分为> 120的蛋白，当核蛋白（NCL）下调时，ALV gp85 mRNA的转录显著增加。通过结合sirna对NCL的干扰效果进行优化，我们发现下调NCL可显著提高LTR的转录活性和U3的增强子能力，进而增强病毒蛋白的表达。相反，过表达NCL显著降低了LTR的转录活性、U3的增强子能力和病毒蛋白的表达水平。这些数据表明NCL对抑制ALV复制至关重要，并从新的角度为开发有效的抗逆转录病毒策略奠定了分子基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Veterinary microbiology 农林科学-兽医学

CiteScore

5.90

自引率

6.10%

发文量

221

审稿时长

52 days

期刊介绍： Veterinary Microbiology is concerned with microbial (bacterial, fungal, viral) diseases of domesticated vertebrate animals (livestock, companion animals, fur-bearing animals, game, poultry, fish) that supply food, other useful products or companionship. In addition, Microbial diseases of wild animals living in captivity, or as members of the feral fauna will also be considered if the infections are of interest because of their interrelation with humans (zoonoses) and/or domestic animals. Studies of antimicrobial resistance are also included, provided that the results represent a substantial advance in knowledge. Authors are strongly encouraged to read - prior to submission - the Editorials (''Scope or cope'' and ''Scope or cope II'') published previously in the journal. The Editors reserve the right to suggest submission to another journal for those papers which they feel would be more appropriate for consideration by that journal. Original research papers of high quality and novelty on aspects of control, host response, molecular biology, pathogenesis, prevention, and treatment of microbial diseases of animals are published. Papers dealing primarily with immunology, epidemiology, molecular biology and antiviral or microbial agents will only be considered if they demonstrate a clear impact on a disease. Papers focusing solely on diagnostic techniques (such as another PCR protocol or ELISA) will not be published - focus should be on a microorganism and not on a particular technique. Papers only reporting microbial sequences, transcriptomics data, or proteomics data will not be considered unless the results represent a substantial advance in knowledge. Drug trial papers will be considered if they have general application or significance. Papers on the identification of microorganisms will also be considered, but detailed taxonomic studies do not fall within the scope of the journal. Case reports will not be published, unless they have general application or contain novel aspects. Papers of geographically limited interest, which repeat what had been established elsewhere will not be considered. The readership of the journal is global.