In vivo translational efficiency of different hepatitis C virus 5'-UTRs

被引:39
作者
Buratti, E
Gerotto, M
Pontisso, P
Alberti, A
Tisminetzky, SG
Baralle, FE
机构
[1] INT CTR GENET ENGN & BIOTECHNOL,I-34012 TRIESTE,ITALY
[2] UNIV PADUA,MED CLIN 2,PADUA,ITALY
关键词
hepatitis C virus; genotype; 5'-untranslated region; translation initiation efficiency;
D O I
10.1016/S0014-5793(97)00715-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Initiation of translation in hepatitis C virus (HCV) is dependent on the presence of an internal ribosome entry site (IRES) contained in its 341-nt-long 5'-untranslated region (UTR), This region is very conserved among different isolates and has been used to classify HCV isolates in six different genotypes, These genotypes differ in nucleotide sequence that generally preserve the IRES structure, However, the small differences seen may be biologically and clinically significant as the HCV strains seem to differ from each other in several important ways, such as the behaviour of the viral infection and the response to interferon therapy, Therefore, differences in translational initiation efficiency amongst the various genotypes could provide an explanation for these phenomena, Using a bicistronic expression system we have compared the in vivo translational ability of the three most common European genotypes of HCV (1, 2, and 3), The results show that genotype 3 is less able than 1 and 2 to promote translation initiation, In addition, by site-directed mutagenesis of the sequence of the IRES domain III apical stem loop structure, we have shown that the conservation of the primary nucleotide sequence and not only the structure, is important for the conservation of IRES function. (C) 1997 Federation of European Biochemical Societies.
引用
收藏
页码:275 / 280
页数:6
相关论文
共 31 条
  • [1] INTERACTION OF POLYPYRIMIDINE TRACT-BINDING PROTEIN WITH THE 5'-NONCODING REGION OF THE HEPATITIS-C VIRUS-RNA GENOME AND ITS FUNCTIONAL REQUIREMENT IN INTERNAL INITIATION OF TRANSLATION
    ALI, N
    SIDDIQUI, A
    [J]. JOURNAL OF VIROLOGY, 1995, 69 (10) : 6367 - 6375
  • [2] Ausubel FM, 1995, SHORT PROTOCOLS MOL
  • [3] Comparison of picornaviral IRES-driven internal initiation of translation in cultured cells of different origins
    Borman, AM
    LeMercier, P
    Girard, M
    Kean, KM
    [J]. NUCLEIC ACIDS RESEARCH, 1997, 25 (05) : 925 - 932
  • [4] SECONDARY STRUCTURE OF THE 5' NONTRANSLATED REGIONS OF HEPATITIS-C VIRUS AND PESTIVIRUS GENOMIC RNAS
    BROWN, EA
    ZHANG, HC
    PING, LH
    LEMON, SM
    [J]. NUCLEIC ACIDS RESEARCH, 1992, 20 (19) : 5041 - 5045
  • [5] SEQUENCE-ANALYSIS OF THE 5' NONCODING REGION OF HEPATITIS-C VIRUS
    BUKH, J
    PURCELL, RH
    MILLER, RH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (11) : 4942 - 4946
  • [6] CERINO A, 1993, J IMMUNOL, V151, P7005
  • [7] ANALYSIS OF A NEW HEPATITIS-C VIRUS TYPE AND ITS PHYLOGENETIC RELATIONSHIP TO EXISTING VARIANTS
    CHAN, SW
    MCOMISH, F
    HOLMES, EC
    DOW, B
    PEUTHERER, JF
    FOLLETT, E
    YAP, PL
    SIMMONDS, P
    [J]. JOURNAL OF GENERAL VIROLOGY, 1992, 73 : 1131 - 1141
  • [8] ISOLATION OF A CDNA CLONE DERIVED FROM A BLOOD-BORNE NON-A, NON-B VIRAL-HEPATITIS GENOME
    CHOO, QL
    KUO, G
    WEINER, AJ
    OVERBY, LR
    BRADLEY, DW
    HOUGHTON, M
    [J]. SCIENCE, 1989, 244 (4902) : 359 - 362
  • [9] GENETIC ORGANIZATION AND DIVERSITY OF THE HEPATITIS-C VIRUS
    CHOO, QL
    RICHMAN, KH
    HAN, JH
    BERGER, K
    LEE, C
    DONG, C
    GALLEGOS, C
    COIT, D
    MEDINASELBY, A
    BARR, PJ
    WEINER, AJ
    BRADLEY, DW
    KUO, G
    HOUGHTON, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (06) : 2451 - 2455
  • [10] THERE ARE 2 MAJOR TYPES OF HEPATITIS-C VIRUS IN JAPAN
    ENOMOTO, N
    TAKADA, A
    NAKAO, T
    DATE, T
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 170 (03) : 1021 - 1025