Extracellular vesicles engineered to directly target encephalomyocarditis virus ameliorates multi-organ viremia in a lethal infection model

IF 2.7 2区农林科学 Q3 MICROBIOLOGY Veterinary microbiology Pub Date : 2025-03-03 DOI:10.1016/j.vetmic.2025.110448

Jiayu Yue , Yanmei Yang , Adi Idris , Wenjing Jin , Yaxin Zhang , Yongfang Chen , Xiangrong Li , Huixia Li , Shasha Li , Yanqiao Wen , Ruofei Feng , Jingying Xie

{"title":"Extracellular vesicles engineered to directly target encephalomyocarditis virus ameliorates multi-organ viremia in a lethal infection model","authors":"Jiayu Yue , Yanmei Yang , Adi Idris , Wenjing Jin , Yaxin Zhang , Yongfang Chen , Xiangrong Li , Huixia Li , Shasha Li , Yanqiao Wen , Ruofei Feng , Jingying Xie","doi":"10.1016/j.vetmic.2025.110448","DOIUrl":null,"url":null,"abstract":"<div><div>The outbreak and prevalence of encephalomyocarditis virus (EMCV) causes significant global mortality and morbidity to the pig industry. Though the current and most effective approach to control EMCV outbreak are done through inactivated vaccines, we have yet to see an effective antiviral agent that directly targets EMCV. Here, we present a molecular therapy consisting of extracellular vesicles (EVs) decorated with EMCV-specific single-chain variable fragment (scFv), engineered on the external loop of the EVS transmembrane domain CD63. These EMCV-scFv enriched EVs directly neutralizes infectious EMCV, thereby inhibiting viral proliferation <em>in vitro</em>. Importantly, we demonstrate that systemic delivery of these EVs reduced multi-organ viremia and clinically rescued EMCV infected mice <em>in vivo</em>. This is the first demonstration of the use of direct acting molecularly engineered EVs to target EMCV infection.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"304 ","pages":"Article 110448"},"PeriodicalIF":2.7000,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary microbiology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378113525000835","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The outbreak and prevalence of encephalomyocarditis virus (EMCV) causes significant global mortality and morbidity to the pig industry. Though the current and most effective approach to control EMCV outbreak are done through inactivated vaccines, we have yet to see an effective antiviral agent that directly targets EMCV. Here, we present a molecular therapy consisting of extracellular vesicles (EVs) decorated with EMCV-specific single-chain variable fragment (scFv), engineered on the external loop of the EVS transmembrane domain CD63. These EMCV-scFv enriched EVs directly neutralizes infectious EMCV, thereby inhibiting viral proliferation in vitro. Importantly, we demonstrate that systemic delivery of these EVs reduced multi-organ viremia and clinically rescued EMCV infected mice in vivo. This is the first demonstration of the use of direct acting molecularly engineered EVs to target EMCV infection.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

直接靶向脑心肌炎病毒的细胞外囊泡改善了致死性感染模型中的多器官病毒血症

脑心肌炎病毒（EMCV）的爆发和流行对全球养猪业造成了重大的死亡率和发病率。虽然目前控制EMCV爆发的最有效方法是通过灭活疫苗，但我们尚未看到直接针对EMCV的有效抗病毒药物。在这里，我们提出了一种分子疗法，由细胞外囊泡（EVs）修饰emcv特异性单链可变片段（scFv）组成，在EVs跨膜结构域CD63的外环上进行工程设计。这些富含EMCV- scfv的ev直接中和感染性EMCV，从而在体外抑制病毒增殖。重要的是，我们证明了这些ev的全身递送减少了多器官病毒血症，并在临床上拯救了体内感染EMCV的小鼠。这是首次使用直接作用的分子工程ev来靶向EMCV感染。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

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.