MicroRNA-122 Regulation of HCV Infections: Insights from Studies of MiR-122-Independent Replication

Overview

Journal Pathogens

Date 2022 Sep 23

PMID 36145436

Authors

Mamata Panigrahi

Michael A Palmer

Joyce A Wilson

Affiliations

Soon will be listed here.

Abstract

Despite the advancement in antiviral therapy, Hepatitis C remains a global health challenge and one of the leading causes of hepatitis related deaths worldwide. Hepatitis C virus, the causative agent, is a positive strand RNA virus that requires a liver specific microRNA called miR-122 for its replication. Unconventional to the canonical role of miRNAs in translation suppression by binding to 3'Untranslated Region (UTR) of messenger RNAs, miR-122 binds to two sites on the 5'UTR of viral genome and promotes viral propagation. In this review, we describe the unique relationship between the liver specific microRNA and HCV, the current knowledge on the mechanisms by which the virus uses miR-122 to promote the virus life cycle, and how miR-122 impacts viral tropism and pathogenesis. We will also discuss the use of anti-miR-122 therapy and its impact on viral evolution of miR-122-independent replication. This review further provides insight into how viruses manipulate host factors at the initial stage of infection to establish a successful infection.

Citing Articles

The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.

Yuan H, Xu R, Li S, Zheng M, Tong Q, Xiang M MedComm (2020). 2025; 6(3):e70121.

PMID: 40060195 PMC: 11890166. DOI: 10.1002/mco2.70121.

The Role of MicroRNAs in Liver Functioning: from Biogenesis to Therapeutic Approaches (Review).

Kozlov D, Rodimova S, Kuznetsova D Sovrem Tekhnologii Med. 2025; 15(5):54-79.

PMID: 39967915 PMC: 11832066. DOI: 10.17691/stm2023.15.5.06.

Development and characterization of a miRNA-responsive circular RNA expression system with cell type specificity.

Ma Y, Mao Y, Luo S, Zuo W, Gao P, Ying B Mol Ther Nucleic Acids. 2025; 36(1):102450.

PMID: 39967851 PMC: 11834102. DOI: 10.1016/j.omtn.2025.102450.

MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products-A Prospective Analysis.

Niazi S, Magoola M Int J Mol Sci. 2024; 25(23.

PMID: 39684593 PMC: 11641023. DOI: 10.3390/ijms252312883.

Extracellular Vesicles in Viral Liver Diseases.

Kouroumalis E, Tsomidis I, Voumvouraki A Viruses. 2024; 16(11).

PMID: 39599900 PMC: 11598962. DOI: 10.3390/v16111785.

References

Schult P, Roth H, Adams R, Mas C, Imbert L, Orlik C . microRNA-122 amplifies hepatitis C virus translation by shaping the structure of the internal ribosomal entry site. Nat Commun. 2018; 9(1):2613. PMC: 6031695. DOI: 10.1038/s41467-018-05053-3. View

Shimakami T, Yamane D, Welsch C, Hensley L, Jangra R, Lemon S . Base pairing between hepatitis C virus RNA and microRNA 122 3' of its seed sequence is essential for genome stabilization and production of infectious virus. J Virol. 2012; 86(13):7372-83. PMC: 3416334. DOI: 10.1128/JVI.00513-12. View

Thakral S, Ghoshal K . miR-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as miRNA mimic and antimir. Curr Gene Ther. 2014; 15(2):142-50. PMC: 4439190. DOI: 10.2174/1566523214666141224095610. View

Walsh D, Mathews M, Mohr I . Tinkering with translation: protein synthesis in virus-infected cells. Cold Spring Harb Perspect Biol. 2012; 5(1):a012351. PMC: 3579402. DOI: 10.1101/cshperspect.a012351. View

Vermehren J, Sarrazin C . New HCV therapies on the horizon. Clin Microbiol Infect. 2010; 17(2):122-34. DOI: 10.1111/j.1469-0691.2010.03430.x. View

Conrad K, Niepmann M . The role of microRNAs in hepatitis C virus RNA replication. Arch Virol. 2013; 159(5):849-62. DOI: 10.1007/s00705-013-1883-4. View

Wienholds E, Kloosterman W, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E . MicroRNA expression in zebrafish embryonic development. Science. 2005; 309(5732):310-1. DOI: 10.1126/science.1114519. View

Li Y, Yamane D, Lemon S . Dissecting the roles of the 5' exoribonucleases Xrn1 and Xrn2 in restricting hepatitis C virus replication. J Virol. 2015; 89(9):4857-65. PMC: 4403451. DOI: 10.1128/JVI.03692-14. View

Tsai W, Hsu S, Hsu C, Lai T, Chen S, Shen R . MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest. 2012; 122(8):2884-97. PMC: 3408747. DOI: 10.1172/JCI63455. View

10.

Chahal J, Gebert L, Gan H, Camacho E, Gunsalus K, MacRae I . miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5' terminus. Nucleic Acids Res. 2019; 47(10):5307-5324. PMC: 6547439. DOI: 10.1093/nar/gkz194. View

11.

Pinzani P, Salvianti F, Pazzagli M, Orlando C . Circulating nucleic acids in cancer and pregnancy. Methods. 2010; 50(4):302-7. DOI: 10.1016/j.ymeth.2010.02.004. View

12.

Sarnow P, Sagan S . Unraveling the Mysterious Interactions Between Hepatitis C Virus RNA and Liver-Specific MicroRNA-122. Annu Rev Virol. 2016; 3(1):309-332. DOI: 10.1146/annurev-virology-110615-042409. View

13.

. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol. 2017; 2(3):161-176. DOI: 10.1016/S2468-1253(16)30181-9. View

14.

Drexler J, Corman V, Muller M, Lukashev A, Gmyl A, Coutard B . Evidence for novel hepaciviruses in rodents. PLoS Pathog. 2013; 9(6):e1003438. PMC: 3688547. DOI: 10.1371/journal.ppat.1003438. View

15.

Chung R . Acute hepatitis C virus infection. Clin Infect Dis. 2005; 41 Suppl 1:S14-7. DOI: 10.1086/429490. View

16.

Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T . Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002; 12(9):735-9. DOI: 10.1016/s0960-9822(02)00809-6. View

17.

Wilson J, Zhang C, Huys A, Richardson C . Human Ago2 is required for efficient microRNA 122 regulation of hepatitis C virus RNA accumulation and translation. J Virol. 2010; 85(5):2342-50. PMC: 3067765. DOI: 10.1128/JVI.02046-10. View

18.

Amador-Canizares Y, Bernier A, Wilson J, Sagan S . miR-122 does not impact recognition of the HCV genome by innate sensors of RNA but rather protects the 5' end from the cellular pyrophosphatases, DOM3Z and DUSP11. Nucleic Acids Res. 2018; 46(10):5139-5158. PMC: 6007490. DOI: 10.1093/nar/gky273. View

19.

Thibault P, Huys A, Amador-Canizares Y, Gailius J, Pinel D, Wilson J . Regulation of Hepatitis C Virus Genome Replication by Xrn1 and MicroRNA-122 Binding to Individual Sites in the 5' Untranslated Region. J Virol. 2015; 89(12):6294-311. PMC: 4474307. DOI: 10.1128/JVI.03631-14. View

20.

Roberts A, Lewis A, Jopling C . miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components. Nucleic Acids Res. 2011; 39(17):7716-29. PMC: 3177192. DOI: 10.1093/nar/gkr426. View