Quasispecies Changes with Distinctive Point Mutations in the Hepatitis C Virus Internal Ribosome Entry Site (IRES) Derived from PBMCs and Plasma

Overview

Journal Adv Virol

Publisher Wiley

Specialty Microbiology

Date 2018 Dec 25

PMID 30581467

Citations 4

Authors

Luca Mercuri

Emma C Thomson

Joseph Hughes

Peter Karayiannis

Affiliations

Soon will be listed here.

Abstract

The 5' untranslated region (UTR) of the hepatitis C virus (HCV) genome contains the internal ribosome entry site (IRES), a highly conserved RNA structure essential for cap-independent translation of the viral polyprotein. HCV, apart from the liver, is thought to be associated with lymphocyte subpopulations of peripheral blood mononuclear cells (PBMCs), in lymph nodes and brain tissue. In this study, RT-PCR, cloning, and sequence analysis were employed to investigate the quasispecies nature of the 5'UTR following extraction of viral RNA from PBMCs and plasma of HCV infected individuals. The nucleotide variation between IRES-derived sequences from PBMCs and plasma indicated the existence of polymorphic sites within the IRES. HCV isolates had divergent variants with unique mutations particularly at positions 107, 204, and 243 of the IRES. Most of the PBMC-derived sequences contained an A-A-A variant at these positions. The mutations associated with the IRESes suggested the presence of unique quasispecies populations in PBMCs compared with plasma.

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References

Honda M, Rijnbrand R, Abell G, Kim D, Lemon S . Natural variation in translational activities of the 5' nontranslated RNAs of hepatitis C virus genotypes 1a and 1b: evidence for a long-range RNA-RNA interaction outside of the internal ribosomal entry site. J Virol. 1999; 73(6):4941-51. PMC: 112538. DOI: 10.1128/JVI.73.6.4941-4951.1999. View

Psaridi L, Georgopoulou U, Varaklioti A, Mavromara P . Mutational analysis of a conserved tetraloop in the 5' untranslated region of hepatitis C virus identifies a novel RNA element essential for the internal ribosome entry site function. FEBS Lett. 1999; 453(1-2):49-53. DOI: 10.1016/s0014-5793(99)00662-6. View

Roque Afonso A, Jiang J, Penin F, Tareau C, Samuel D, Petit M . Nonrandom distribution of hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cell subsets. J Virol. 1999; 73(11):9213-21. PMC: 112955. DOI: 10.1128/JVI.73.11.9213-9221.1999. View

Laskus T, Radkowski M, Wang L, Nowicki M, Rakela J . Uneven distribution of hepatitis C virus quasispecies in tissues from subjects with end-stage liver disease: confounding effect of viral adsorption and mounting evidence for the presence of low-level extrahepatic replication. J Virol. 2000; 74(2):1014-7. PMC: 111624. DOI: 10.1128/jvi.74.2.1014-1017.2000. View

Lerat H, Shimizu Y, Lemon S . Cell type-specific enhancement of hepatitis C virus internal ribosome entry site-directed translation due to 5' nontranslated region substitutions selected during passage of virus in lymphoblastoid cells. J Virol. 2000; 74(15):7024-31. PMC: 112219. DOI: 10.1128/jvi.74.15.7024-7031.2000. View

Jubin R, Vantuno N, Kieft J, Murray M, Doudna J, Lau J . Hepatitis C virus internal ribosome entry site (IRES) stem loop IIId contains a phylogenetically conserved GGG triplet essential for translation and IRES folding. J Virol. 2000; 74(22):10430-7. PMC: 110917. DOI: 10.1128/jvi.74.22.10430-10437.2000. View

Kieft J, Zhou K, Jubin R, Doudna J . Mechanism of ribosome recruitment by hepatitis C IRES RNA. RNA. 2001; 7(2):194-206. PMC: 1370078. DOI: 10.1017/s1355838201001790. View

Radkowski M, Wilkinson J, Nowicki M, Adair D, Vargas H, Ingui C . Search for hepatitis C virus negative-strand RNA sequences and analysis of viral sequences in the central nervous system: evidence of replication. J Virol. 2001; 76(2):600-8. PMC: 136845. DOI: 10.1128/jvi.76.2.600-608.2002. View

Kalliampakou K, Psaridi-Linardaki L, Mavromara P . Mutational analysis of the apical region of domain II of the HCV IRES. FEBS Lett. 2002; 511(1-3):79-84. DOI: 10.1016/s0014-5793(01)03300-2. View

10.

Lytle J, Wu L, Robertson H . Domains on the hepatitis C virus internal ribosome entry site for 40s subunit binding. RNA. 2002; 8(8):1045-55. PMC: 1370315. DOI: 10.1017/s1355838202029965. View

11.

Laporte J, Bain C, Maurel P, Inchauspe G, Agut H, Cahour A . Differential distribution and internal translation efficiency of hepatitis C virus quasispecies present in dendritic and liver cells. Blood. 2002; 101(1):52-7. DOI: 10.1182/blood-2002-03-0818. View

12.

Bukh J, Purcell R, Miller R . Sequence analysis of the 5' noncoding region of hepatitis C virus. Proc Natl Acad Sci U S A. 1992; 89(11):4942-6. PMC: 49204. DOI: 10.1073/pnas.89.11.4942. View

13.

Ducoulombier D, Roque-Afonso A, Di Liberto G, Penin F, Kara R, Richard Y . Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes. Hepatology. 2004; 39(3):817-25. DOI: 10.1002/hep.20087. View

14.

Forton D, Karayiannis P, Mahmud N, Taylor-Robinson S, Thomas H . Identification of unique hepatitis C virus quasispecies in the central nervous system and comparative analysis of internal translational efficiency of brain, liver, and serum variants. J Virol. 2004; 78(10):5170-83. PMC: 400349. DOI: 10.1128/jvi.78.10.5170-5183.2004. View

15.

Mathews D, Disney M, Childs J, Schroeder S, Zuker M, Turner D . Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc Natl Acad Sci U S A. 2004; 101(19):7287-92. PMC: 409911. DOI: 10.1073/pnas.0401799101. View

16.

Radkowski M, Gallegos-Orozco J, Jablonska J, Colby T, Walewska-Zielecka B, Kubicka J . Persistence of hepatitis C virus in patients successfully treated for chronic hepatitis C. Hepatology. 2004; 41(1):106-14. DOI: 10.1002/hep.20518. View

17.

Bare P, Massud I, Parodi C, Belmonte L, Garcia G, Nebel M . Continuous release of hepatitis C virus (HCV) by peripheral blood mononuclear cells and B-lymphoblastoid cell-line cultures derived from HCV-infected patients. J Gen Virol. 2005; 86(Pt 6):1717-1727. DOI: 10.1099/vir.0.80882-0. View

18.

Laletina E, Graifer D, Malygin A, Ivanov A, Shatsky I, Karpova G . Proteins surrounding hairpin IIIe of the hepatitis C virus internal ribosome entry site on the human 40S ribosomal subunit. Nucleic Acids Res. 2006; 34(7):2027-36. PMC: 1435985. DOI: 10.1093/nar/gkl155. View

19.

Pal S, Sullivan D, Kim S, Lai K, Kae J, Cotler S . Productive replication of hepatitis C virus in perihepatic lymph nodes in vivo: implications of HCV lymphotropism. Gastroenterology. 2006; 130(4):1107-16. DOI: 10.1053/j.gastro.2005.12.039. View

20.

Gallegos-Orozco J, Arenas J, Vargas H, Kibler K, Wilkinson J, Nowicki M . Selection of different 5' untranslated region hepatitis C virus variants during post-transfusion and post-transplantation infection. J Viral Hepat. 2006; 13(7):489-98. DOI: 10.1111/j.1365-2893.2006.00724.x. View