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The **Hepatitis C virus 5′ untranslated region (HCV 5′ UTR)** is a highly conserved non-coding RNA segment of approximately 340 nucleotides located at the 5′ terminus of the viral RNA genome. It is crucial for regulating both cap-independent translation of viral proteins through an internal ribosome entry site (IRES) and for viral RNA replication[2][3][5][9]. The IRES comprises highly structured stem-loop domains that mediate recruitment of cellular translation machinery independently of the host mRNA cap, enabling HCV to efficiently translate its polyprotein[5][8][9]. Additionally, the 5′ UTR contains sequences necessary for the initiation and regulation of viral RNA replication, as well as binding sites for host factors such as miR-122, which is essential for efficient viral genome stability and replication[2]. The region is a preferred target for molecular diagnostics due to its sequence conservation across all HCV genotypes[6][7]. Pharmacological targeting of this region is possible through antisense oligonucleotides, siRNAs, or by blocking critical RNA-host protein interactions; however, therapeutic interventions must consider viral escape, host off-targets, and essential host pathways such as those modulated by miR-122[2].
Inhibition of IRES-mediated translation (small molecules or oligonucleotides); Disruption of miR-122/HCV 5′ UTR interaction (e.g., Miravirsen); Steric hindrance of RNA-protein interactions
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