Comparative Analysis of Translation Efficiencies of Hepatitis C Virus 5′ Untranslated Regions among Intraindividual Quasispecies Present in Chronic Infection: Opposite Behaviors Depending on Cell Type

ABSTRACT Hepatitis C virus (HCV) RNA translation initiation is dependent on the presence of an internal ribosome entry site (IRES) that is found mostly in its 5′ untranslated region (5′ UTR). While exhibiting the most highly conserved sequence within the genome, the 5′ UTR accumulates small differences, which may be of biological and clinical importance. In this study, using a bicistronic dual luciferase expression system, we have examined the sequence of 5′ UTRs from quasispecies characterized in the serum of a patient chronically infected with HCV genotype 1a and its corresponding translational activity. Sequence heterogeneity between IRES elements led to important changes in their translation efficiency both in vitro and in different cell cultures lines, implying that interactions of RNA with related transacting factors may vary according to cell type. These data suggest that variants occasionally carried by the serum prior to reinfection could be selected toward different compartments of the same infected organism, thus favoring the hypothesis of HCV multiple tropism.

[1]  F. Penin,et al.  Nonrandom Distribution of Hepatitis C Virus Quasispecies in Plasma and Peripheral Blood Mononuclear Cell Subsets , 1999, Journal of Virology.

[2]  R. Purcell,et al.  Quasispecies in viral persistence and pathogenesis of hepatitis C virus. , 1999, Trends in microbiology.

[3]  Mengji Lu,et al.  Selection of genetic variants of the 5′ noncoding region of hepatitis C virus occurs only in patients responding to interferon α therapy , 1999, Journal of medical virology.

[4]  J Y Lau,et al.  The hepatitis C virus internal ribosome entry site adopts an ion-dependent tertiary fold. , 1999, Journal of molecular biology.

[5]  M. Honda,et al.  Quasispecies of hepatitis C virus in serum and in three different parts of the liver of patients with chronic hepatitis , 1999, Hepatology.

[6]  U. Georgopoulou,et al.  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 , 1999, FEBS letters.

[7]  Desok Kim,et al.  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 , 1999, Journal of Virology.

[8]  R. Elliott,et al.  Alterations to both the Primary and Predicted Secondary Structure of Stem-Loop IIIc of the Hepatitis C Virus 1b 5′ Untranslated Region (5′UTR) Lead to Mutants Severely Defective in Translation Which Cannot Be Complemented intrans by the Wild-Type 5′UTR Sequence , 1999, Journal of Virology.

[9]  J. Rakela,et al.  Differences between hepatitis C virus 5' untranslated region quasispecies in serum and liver. , 1999, The Journal of general virology.

[10]  M. Honda,et al.  A Phylogenetically Conserved Stem-Loop Structure at the 5′ Border of the Internal Ribosome Entry Site of Hepatitis C Virus Is Required for Cap-Independent Viral Translation , 1999, Journal of Virology.

[11]  H. Agut,et al.  Yellow fever 5' noncoding region as a potential element to improve hepatitis C virus production through modification of translational control. , 1998, Biochemical and Biophysical Research Communications - BBRC.

[12]  R. Elliott,et al.  Translation efficiencies of the 5' untranslated region from representatives of the six major genotypes of hepatitis C virus using a novel bicistronic reporter assay system. , 1998, The Journal of general virology.

[13]  Emanuele Buratti,et al.  Functional analysis of the interaction between HCV 5'UTR and putative subunits of eukaryotic translation initiation factor eIF3 , 1998, Nucleic Acids Res..

[14]  C. Hellen,et al.  Specific Interaction of Eukaryotic Translation Initiation Factor 3 with the 5′ Nontranslated Regions of Hepatitis C Virus and Classical Swine Fever Virus RNAs , 1998, Journal of Virology.

[15]  E. Gowans,et al.  Identification of novel sequences at the 5′ terminus of the hepatitis C virus genome , 1998, Journal of viral hepatitis.

[16]  N. Enomoto,et al.  Nucleotide sequence variations in the internal ribosome entry site of hepatitis C virus‐1b: No association with efficacy of interferon therapy or serum HCV‐RNA levels , 1997, Hepatology.

[17]  R. Purcell,et al.  Sequence analysis of the hepatitis C virus genome recovered from serum, liver, and peripheral blood mononuclear cells of infected chimpanzees , 1997, Journal of virology.

[18]  C. Rice,et al.  Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. , 1997, Science.

[19]  A. Alberti,et al.  In vivo translational efficiency of different hepatitis C virus 5′‐UTRs , 1997, FEBS letters.

[20]  A. Nomoto,et al.  Genetic analysis of internal ribosomal entry site on hepatitis C virus RNA: implication for involvement of the highly ordered structure and cell type-specific transacting factors. , 1997, Virology.

[21]  Philippe Le Mercier,et al.  Comparison of picornaviral IRES-driven internal initiation of translation in cultured cells of different origins. , 1997, Nucleic acids research.

[22]  M. Honda,et al.  Stability of a stem-loop involving the initiator AUG controls the efficiency of internal initiation of translation on hepatitis C virus RNA. , 1996, RNA.

[23]  E. Wimmer,et al.  Poliovirus chimeras replicating under the translational control of genetic elements of hepatitis C virus reveal unusual properties of the internal ribosomal entry site of hepatitis C virus. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Jackson,et al.  Unique features of internal initiation of hepatitis C virus RNA translation. , 1995, The EMBO journal.

[25]  P. Simmonds,et al.  Variation of the hepatitis C virus 5' non-coding region: implications for secondary structure, virus detection and typing. The International HCV Collaborative Study Group. , 1995, The Journal of general virology.

[26]  A. Siddiqui,et al.  A conserved helical element is essential for internal initiation of translation of hepatitis C virus RNA , 1994, Journal of virology.

[27]  S. Fukushi,et al.  Complete 5' noncoding region is necessary for the efficient internal initiation of hepatitis C virus RNA. , 1994, Biochemical and biophysical research communications.

[28]  A. Siddiqui,et al.  Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism , 1993, Journal of virology.

[29]  A. Nomoto,et al.  Internal ribosome entry site within hepatitis C virus RNA , 1992, Journal of virology.

[30]  S. Lemon,et al.  Internal ribosome entry site-mediated translation in hepatitis C virus replication. , 2000, Current topics in microbiology and immunology.

[31]  J. Sánchez-Tapias,et al.  Internal initiation of translation efficiency in different hepatitis C genotypes isolated from interferon treated patients , 1999, Archives of Virology.

[32]  R. Jackson,et al.  A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initiation of hepatitis C and classical swine fever virus RNAs. , 1998, Genes & development.