¹Laboratoire des Virus Entérotropes et Stratégies Antivirales, Département de Virologie, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France

Correspondence: Florence Colbère-Garapin, Fax: (33) 1 45 68 87 80. E-mail: fcolbere@pasteur.fr

^*Present address: Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris, France.

Received 11 May 2005; Revised 7 July 2005; Accepted 31 July 2005.

Abstract

Small interfering RNAs (siRNAs) have been developed as antiviral agents for mammalian cells. The capacity of specific siRNAs to prevent virus infections has been demonstrated, and there is evidence that these new antiviral agents could have a partial therapeutic effect a few days after infection. We investigated the possibility of curing a persistent infection, several months after becoming established, using an in vitro model of persistent poliovirus (PV) infection in HEp-2 cells. Despite high virus titers and the presence of PV mutants, repeated treatment with a mixture of two siRNAs targeting both noncoding and coding regions, one of them in a highly conserved region, resulted in the complete cure of the majority of persistently infected cultures. No escape mutants emerged in treated cultures. The antiviral effect of specific siRNAs, consistent with a mechanism of RNA interference, correlated with a decrease in the amount of viral RNA, until its complete disappearance, resulting in cultures cured of virions and viral RNA.