Wang Xinyu, Terrie Lisanne, Wu Guanghui, Van Damme Els J M, Thorrez Lieven, Fooks Anthony R, Banyard Ashley C, Jochmans Dirk, Neyts Johan
Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, 3000 Leuven, Belgium.
Global Virus Network (GVN), Baltimore, MD 21201, USA.
Pharmaceutics. 2023 Apr 28;15(5):1353. doi: 10.3390/pharmaceutics15051353.
Infection with the rabies virus (RABV) results in a 100% lethal neurological disease once symptoms develop. Post-exposure prophylaxis (PEP) consists of a combination of vaccination and anti-rabies immunoglobulins (RIGs); it is 100% effective if administered early after exposure. Because of its limited availability, alternatives for RIGs are needed. To that end, we evaluated a panel of 33 different lectins for their effect on RABV infection in cell culture. Several lectins, with either mannose or GlcNAc specificity, elicited anti-RABV activity, of which the GlcNAc-specific agglutinin (UDA) was selected for further studies. UDA was found to prevent the entry of the virus into the host cell. To further assess the potential of UDA, a physiologically relevant RABV infection muscle explant model was developed. Strips of dissected swine skeletal muscle that were kept in a culture medium could be productively infected with the RABV. When the infection of the muscle strips was carried out in the presence of UDA, RABV replication was completely prevented. Thus, we developed a physiologically relevant RABV muscle infection model. UDA (i) may serve as a reference for further studies and (ii) holds promise as a cheap and simple-to-produce alternative for RIGs in PEP.
一旦出现症状,感染狂犬病病毒(RABV)会导致100%致死性神经疾病。暴露后预防(PEP)包括疫苗接种和抗狂犬病免疫球蛋白(RIGs)联合使用;如果在暴露后早期进行,其有效性为100%。由于RIGs供应有限,需要其替代品。为此,我们评估了一组33种不同的凝集素对细胞培养中RABV感染的影响。几种具有甘露糖或N-乙酰葡糖胺特异性的凝集素引发了抗RABV活性,其中选择了具有N-乙酰葡糖胺特异性的凝集素(UDA)进行进一步研究。发现UDA可阻止病毒进入宿主细胞。为了进一步评估UDA的潜力,开发了一种生理相关的RABV感染肌肉外植体模型。保存在培养基中的猪骨骼肌切片可被RABV有效感染。当在UDA存在的情况下对肌肉切片进行感染时,RABV复制被完全阻止。因此,我们开发了一种生理相关的RABV肌肉感染模型。UDA(i)可作为进一步研究的参考,(ii)有望作为PEP中RIGs的廉价且易于生产的替代品。
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