Bitko Vira, Musiyenko Alla, Shulyayeva Olena, Barik Sailen
Department of Biochemistry and Molecular Biology (MSB 2370), University of South Alabama, College of Medicine, 307 University Boulevard, Mobile, Alabama 36688-0002, USA.
Nat Med. 2005 Jan;11(1):50-5. doi: 10.1038/nm1164. Epub 2004 Dec 26.
Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are two respiratory pathogens of paramount medical significance that exert high mortality. At present, there is no reliable vaccine or antiviral drug against either virus. Using an RNA interference (RNAi) approach, we show that individual as well as joint infection by RSV and PIV can be specifically prevented and inhibited by short interfering RNAs (siRNAs), instilled intranasally in the mouse, with or without transfection reagents. The degree of protection matched the antiviral activity of the siRNA in cell culture, allowing an avenue for quick screening of an efficacious siRNA. When targeting both viruses in a joint infection, excess of one siRNA moderated the inhibitory effect of the other, suggesting competition for the RNAi machinery. Our results suggest that, if properly designed, low dosages of inhaled siRNA might offer a fast, potent and easily administrable antiviral regimen against respiratory viral diseases in humans.
呼吸道合胞病毒（RSV）和副流感病毒（PIV）是两种具有极高医学重要性的呼吸道病原体，会导致高死亡率。目前，尚无针对这两种病毒的可靠疫苗或抗病毒药物。我们采用RNA干扰（RNAi）方法表明，通过鼻内滴注（无论是否使用转染试剂）将小干扰RNA（siRNA）注入小鼠体内，可特异性预防和抑制RSV和PIV的单独感染以及联合感染。保护程度与siRNA在细胞培养中的抗病毒活性相匹配，这为快速筛选有效的siRNA提供了一条途径。当针对联合感染中的两种病毒时，一种siRNA过量会减弱另一种的抑制作用，这表明存在对RNAi机制的竞争。我们的结果表明，如果设计得当，低剂量吸入式siRNA可能为人类呼吸道病毒性疾病提供一种快速、有效且易于给药的抗病毒方案。
