Antiviral role of cholesterol 25-hydroxylase in inhibiting porcine circovirus 3 replication

IF 2.4 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology Pub Date : 2024-10-22 DOI:10.1016/j.vetmic.2024.110284

Baoge Zhang, Lumen Chao, Zhendong Wang, Hao Yu, Yufeng Li

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引用次数: 0

Abstract

Cholesterol 25-hydroxylase (CH25H) has significant antiviral effects through the production of 25-hydroxycholesterol (25HC). In this study, we investigated the effects of CH25H, its catalytic product 25HC, and its catalytic mutant lacking hydroxylase activity (CH25H-M) on porcine circovirus 3 (PCV3) replication. By transfecting PCV3 persistently infected PK-15 cells with the pCAGGS-CH25H-Flag plasmid, the results demonstrated that overexpression of CH25H significantly inhibited PCV3 Cap protein expression, Cap mRNA levels, and viral titers in a dose-dependent manner. Moreover, its catalytic product 25HC inhibited PCV3 replication in PK-15 cells at concentrations below 10 µM without affecting cell viability. In contrast, knockdown of endogenous CH25H using small interfering RNA (siRNA) enhanced PCV3 replication, further confirming its antiviral role. Interestingly, the CH25H-M mutant also exhibited inhibitory effects on PCV3 replication, although the inhibition was much less effective compared with CH25H. In conclusion, CH25H plays a critical role in regulating PCV3 replication, and its antiviral effect is not entirely dependent on its enzymatic activity. These findings provide new insights into both the enzymatic and non-enzymatic antiviral mechanisms of CH25H and revealed some mechanistic immune evasion for PCV3.

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胆固醇 25- 羟化酶在抑制猪圆环病毒 3 复制中的抗病毒作用。

胆固醇 25- 羟化酶（CH25H）通过产生 25- 羟基胆固醇（25HC）具有显著的抗病毒作用。本研究调查了 CH25H、其催化产物 25HC 及其缺乏羟化酶活性的催化突变体（CH25H-M）对猪圆环病毒 3（PCV3）复制的影响。通过用 pCAGGS-CH25H-Flag 质粒转染 PCV3 持续感染的 PK-15 细胞，结果表明过表达 CH25H 能显著抑制 PCV3 Cap 蛋白的表达、Cap mRNA 水平和病毒滴度，且呈剂量依赖性。此外，其催化产物 25HC 在浓度低于 10 µM 时可抑制 PCV3 在 PK-15 细胞中的复制，且不影响细胞活力。相反，使用小干扰 RNA（siRNA）敲除内源性 CH25H 会增强 PCV3 复制，进一步证实了它的抗病毒作用。有趣的是，CH25H-M 突变体对 PCV3 复制也有抑制作用，但与 CH25H 相比，抑制效果要差得多。总之，CH25H 在调节 PCV3 复制过程中起着关键作用，其抗病毒作用并不完全依赖于其酶活性。这些发现为研究 CH25H 的酶和非酶抗病毒机制提供了新的视角，并揭示了 PCV3 的一些免疫逃避机制。

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.