Impact of equine herpesvirus-1 ORF15 (EUL45) on viral replication and neurovirulence

IF 2.4 2区 农林科学 Q3 MICROBIOLOGY Veterinary microbiology Pub Date : 2024-08-22 DOI:10.1016/j.vetmic.2024.110234
Samy Kasem , Mi Htay Htay Yu , Noura Alkhalefa , Emad B. Ata , Mohamed Nayel , Walied Abdo , Ahmed S. Abdel-Moneim , Hideto Fukushi
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Abstract

Equine herpesvirus 1 (EHV-1) causes respiratory illness, fetal loss, perinatal mortality, and myeloencephalopathy. This study investigated ORF15's impact on virus infectivity and neurovirulence. The Ab4p neurovirulent strain of EHV1 was used as a backbone to create Ab4p attB, Ab4p∆ORF15, and Ab4p∆ORF15R chimeras via BAC DNA transfection into RK-13 cells. Viral growth kinetics, plaque size, transcription, and growth were assessed in MDBK cells, mouse neurons, and fetal equine brain cells. Neurovirulence was evaluated post-intranasal inoculation into male CBA/N1 SPF mice, measuring signs, virus titers, and histopathological changes. Deletion of EUL45 (Ab4p-∆EUL45) reduced viral replication efficiency, resulting in decreased release and smaller plaques. EUL45 deletion also upregulated neighbouring genes (EUL46 and EUL44). Ab4p-∆EUL45 exhibited reduced virulence and poor growth in neural cells compared to wild-type viruses. This study sheds light on EUL45's role in EHV-1, viral replication, and regulation of EUL46 and EUL44 expression, suggesting potential as a vaccine candidate.

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马疱疹病毒-1 ORF15 (EUL45) 对病毒复制和神经病毒性的影响
马疱疹病毒 1(EHV-1)会导致呼吸道疾病、胎儿死亡、围产期死亡和髓脑病。本研究调查了 ORF15 对病毒传染性和神经毒力的影响。以 EHV1 的 Ab4p 神经病毒毒株为骨干,通过 BAC DNA 转染 RK-13 细胞制造 Ab4p attB、Ab4p∆ORF15 和 Ab4p∆ORF15R 嵌合体。在 MDBK 细胞、小鼠神经元和胎儿马脑细胞中对病毒的生长动力学、斑块大小、转录和生长进行了评估。在雄性CBA/N1 SPF小鼠体内接种病毒后,通过测量体征、病毒滴度和组织病理学变化来评估神经病毒性。EUL45(Ab4p-ΔEUL45)缺失会降低病毒复制效率,导致释放减少和斑块变小。删除 EUL45 还会上调邻近基因(EUL46 和 EUL44)。与野生型病毒相比,Ab4p-ΔEUL45的毒力减弱,在神经细胞中的生长也很差。这项研究揭示了EUL45在EHV-1、病毒复制以及EUL46和EUL44表达调控中的作用,表明它有可能成为候选疫苗。
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来源期刊
Veterinary microbiology
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.
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