Hepatitis C virus genomic RNA miR-122 binding site 1 (S1) (HCV RNA S1)

The Hepatitis C virus (HCV) genomic RNA miR-122 binding site 1 (S1) is a highly conserved sequence located within the 5' untranslated region (UTR) of the viral genome (Jopling et al., Science, 2005; NIH). Unlike the canonical role of microRNAs in suppressing gene expression, the binding of the liver-specific microRNA-122 (miR-122) to this site is essential for the viral life cycle (Jopling et al., Science, 2005; MDPI). This interaction provides stability to the uncapped viral RNA by protecting it from 5' exonucleolytic degradation by the host enzyme Xrn1 and also facilitates the initiation of viral translation and replication (Li et al., PNAS, 2013; NIH). Because of its critical role in viral persistence, S1 and its interaction with miR-122 have become significant targets for antiviral therapy (Janssen et al., NEJM, 2013; NIH). Therapeutic strategies targeting this site primarily involve antisense oligonucleotides, such as Miravirsen (SPC3649) and RG-101, which sequester miR-122 and prevent it from associating with the viral genome (Santaris Pharma; Regulus Therapeutics). Clinical studies have demonstrated that blocking this interaction leads to a rapid and sustained reduction in viral load across multiple HCV genotypes (Janssen et al., NEJM, 2013; van der Ree et al., Lancet, 2017). However, therapeutic challenges include the potential for viral escape through mutations in the binding site and the risk of off-target effects on host lipid metabolism, which is also regulated by miR-122 (NIH; Regulus Therapeutics). Despite these challenges, targeting the HCV RNA-miR-122 complex remains a potent approach for treating chronic hepatitis C infection (AASLD; NIH).

Other names

Site 1S1miR-122 binding site 1HCV 5' UTR site 1HCV miR-122 S1

Antisense sequestration of host miR-122 to prevent its binding to the viral RNA site, leading to viral RNA degradation and inhibition of replication.