Sleeman Katrina, Stein David A, Tamin Azaibi, Reddish Michael, Iversen Patrick L, Rota Paul A
Measles, Mumps, Rubella, and Herpesviruses Laboratory Branch, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Virus Res. 2009 Mar;140(1-2):49-56. doi: 10.1016/j.virusres.2008.10.018. Epub 2009 Jan 6.
Measles virus (MeV) is a highly contagious human pathogen. Despite the success of measles vaccination programs, measles is still responsible for an estimated 245,000 deaths each year. There are currently no antiviral compounds available for the treatment of measles. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are antisense compounds that enter cells readily and can interfere with mRNA function by steric blocking. A panel of PPMO was designed to target various sequences of MeV RNA that are known to be important for viral replication. Five PPMO, targeting MeV genomic RNA or mRNA, inhibited the replication of MeV, in a dose-responsive and sequence-specific manner in cultured cells. One of the highly active PPMO (PPMO 454), targeting a conserved sequence in the translation start site of the mRNA coding for the nucleocapsid protein, inhibited multiple genotypes of MeV. This report provides evidence that PPMO treatment represents a promising approach for developing antiviral agents against measles and other paramyxoviruses.
麻疹病毒（MeV）是一种极具传染性的人类病原体。尽管麻疹疫苗接种计划取得了成功，但麻疹每年仍导致约24.5万人死亡。目前尚无用于治疗麻疹的抗病毒化合物。肽缀合的磷二酰胺吗啉代寡聚物（PPMO）是一类反义化合物，能够轻易进入细胞，并通过空间位阻干扰mRNA功能。一组PPMO被设计用于靶向已知对病毒复制很重要的MeV RNA的各种序列。五种靶向MeV基因组RNA或mRNA的PPMO，在培养细胞中以剂量反应和序列特异性的方式抑制了MeV的复制。其中一种高活性PPMO（PPMO 454）靶向编码核衣壳蛋白的mRNA翻译起始位点的保守序列，抑制了多种MeV基因型。本报告提供了证据，表明PPMO治疗是开发针对麻疹和其他副粘病毒的抗病毒药物的一种有前景的方法。
