Ren Tongwei, Liu Muyang, Zhou Lingshan, Zhang Liping, Qin Yifeng, Ouyang Kang, Chen Ying, Huang Weijian, Wei Zuzhang
Laboratory of Animal infectious Diseases and molecular Immunology, College of Animal Science and Technology, Guangxi University, Nanning, 530005, China.
Laboratory of Animal infectious Diseases and molecular Immunology, College of Animal Science and Technology, Guangxi University, Nanning, 530005, China; Guangxi Zhuang Autonomous Region Engineering Research Center of Veterinary Biologics, Nanning, 530005, China; Guangxi Key Laboratory of Animal Reproduction, Breeding and Disease Control, Nanning, 530005, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control for Animal Disease, Nanning, 530005, China.
Virology. 2024 Oct;598:110174. doi: 10.1016/j.virol.2024.110174. Epub 2024 Jul 16.
Getah virus (GETV) is a re-emerging mosquito-borne RNA virus that induces fever, hind limb edema, swollen submandibular lymph nodes, and urticaria in horses. In pigs, the virus often results in stillbirths among pregnant sows, and neurological symptoms leading to death in piglets. Currently, there are no specific treatments or drugs available for GETV infection. The use of reporter viruses to monitor viral replication and spread in real-time within infected cells and animals provides a powerful tool for targeting antiviral drugs throughout the viral life cycle. Their fluorescence-tracked characteristics greatly facilitate virus neutralization tests (VNTs). In this study, we engineered two recombinant viruses by inserting different reporter protein genes at the 3' end of the structural protein gene, an unreported location that can accommodate exogenous genes. The rGEEiLOV and rGEEGFP viruses demonstrated genetic stability for at least five passages and replicated at a rate similar to that of the parental virus in BHK-21 cells. The rGEEGFP virus facilitated viral neutralization testing. Additionally, we used the reporter virus rGEEGFP to confirm ivermectin, a broad-spectrum antiparasitic agent, as a potential inhibitor of GETV in vitro. Ivermectin appears to inhibit the early replication stages of the virus and can block cell-to-cell viral transmission. In conclusion, rGEEGFP holds significant potential for antiviral screening to identify specific inhibitors against GETV and for use in viral neutralization tests.
盖塔病毒(GETV)是一种重新出现的蚊媒RNA病毒,可引起马匹发热、后肢水肿、下颌下淋巴结肿大和荨麻疹。在猪身上,该病毒常导致怀孕母猪死胎,以及仔猪出现神经症状并导致死亡。目前,尚无针对GETV感染的特异性治疗方法或药物。利用报告病毒实时监测病毒在受感染细胞和动物体内的复制和传播,为在病毒整个生命周期中靶向抗病毒药物提供了一个强大工具。它们的荧光追踪特性极大地促进了病毒中和试验(VNTs)。在本研究中,我们通过在结构蛋白基因的3'端(一个可容纳外源基因的未报道位置)插入不同的报告蛋白基因,构建了两种重组病毒。rGEEiLOV和rGEEGFP病毒在至少传代五次后表现出遗传稳定性,并且在BHK-21细胞中的复制速率与亲本病毒相似。rGEEGFP病毒促进了病毒中和试验。此外,我们使用报告病毒rGEEGFP证实了广谱抗寄生虫药伊维菌素在体外是GETV的潜在抑制剂。伊维菌素似乎抑制病毒的早期复制阶段,并能阻断病毒的细胞间传播。总之,rGEEGFP在抗病毒筛选以鉴定针对GETV的特异性抑制剂以及用于病毒中和试验方面具有巨大潜力。