用酶促合成的小干扰RNA簇进行单纯疱疹病毒感染的局部治疗
Topical treatment of herpes simplex virus infection with enzymatically created siRNA swarm.
作者信息
Paavilainen Henrik, Lehtinen Jenni, Romanovskaya Alesia, Nygårdas Michaela, Bamford Dennis H, Poranen Minna M, Hukkanen Veijo
机构信息
Department of Virology, University of Turku, Turku, Finland.
Drug Research Doctoral Programme, University of Turku, Turku, Finland.
出版信息
Antivir Ther. 2017;22(7):631-637. doi: 10.3851/IMP3153. Epub 2017 Mar 13.
BACKGROUND
Herpes simplex virus (HSV) is a common human pathogen. Despite current antivirals, it causes a significant medical burden. Drug resistant strains exist and they are especially prevalent in immunocompromised patients and in HSV eye infections. New treatment modalities are needed.
METHODS
BALB/c mice were corneally infected with HSV and subsequently treated with a swarm of enzymatically created, Dicer-substrate small interfering RNA (siRNA) molecules that targeted the HSV gene UL29. Two infection models were used, one in which the infection was predominantly peripheral and another in which it spread to the central nervous system. Mouse survival, as well as viral spread, load, latency and peripheral shedding, was studied.
RESULTS
The anti-HSV-UL29 siRNA swarm alleviated HSV infection symptoms, inhibited viral shedding and replication and had a favourable effect on mouse survival.
CONCLUSIONS
Treatment with anti-HSV-UL29 siRNA swarm reduced symptoms and viral spread in HSV infection of mice and also inhibited local viral replication in mouse corneas.
背景
单纯疱疹病毒（HSV）是一种常见的人类病原体。尽管有目前的抗病毒药物，但它仍造成了重大的医疗负担。耐药菌株存在，且在免疫功能低下的患者和HSV眼部感染中尤为普遍。需要新的治疗方法。
方法
将BALB/c小鼠角膜感染HSV，随后用一群酶促产生的、靶向HSV基因UL29的Dicer底物小干扰RNA（siRNA）分子进行治疗。使用了两种感染模型，一种感染主要为外周性，另一种感染扩散至中枢神经系统。研究了小鼠的存活率以及病毒传播、载量、潜伏期和外周排毒情况。
结果
抗HSV-UL29 siRNA群减轻了HSV感染症状，抑制了病毒排毒和复制，并对小鼠存活率产生了有利影响。
结论
用抗HSV-UL29 siRNA群治疗可减轻小鼠HSV感染的症状和病毒传播，还可抑制小鼠角膜中的局部病毒复制。
Zotero 插件