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

被引:73
作者
Kamoshita, N
TsukiyamaKohara, K
Kohara, M
Nomoto, A
机构
[1] UNIV TOKYO,INST MED SCI,DEPT MICROBIOL,MINATO KU,TOKYO 108,JAPAN
[2] TOKYO METROPOLITAN INST MED SCI,DEPT MICROBIOL,BUNKYO KU,TOKYO 113,JAPAN
关键词
D O I
10.1006/viro.1997.8600
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Hepatitis C virus (HCV) carries an internal ribosomal entry site (IRES) within the 5' portion of the RNA. To identify structures that influence efficiency of the translation initiation, relative activities of modified IRESs were examined by using engineered bicistronic mRNAs, between the two cistrons of which various mutant IRESs were inserted. An [RES derived from genotype 2b is at least two times more efficient than one from genotype Ib in cultured cells. Activity ratios of genotype 2b IRES to Ib IRES differ in magnification among cultured cells, suggesting the difference in assortment of IRES-related host factors among individual cell types. Recombinant IRESs between the genotypes show similar or higher activities compared with 2b IRES in cell-free systems and show intermediate activities in cultured cells. Patterns of relative activities of those IRESs indicate that the IRES activity is not regulated by defined structure(s), although a cluster of different nucleotides is observed in the genome region of nucleotides 176-224 between the two alleles. The results suggest that a highly ordered structure formed by the entire 5' portion of the RNA is important for the IRES activity. The 5' border of HCV IRES was examined by using a series of deletion RNAs in Various systems. The results strongly suggest that the border resides between nucleotide positions 28 and 45. Patterns of relative activities of the deletion IRESs differ in translation systems or cell types. These results imply that interactions of HCV RNA with the related transacting factor(s) may differ in the translation systems or cell types. (C) 1997 Academic Press.
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页码:9 / 18
页数:10
相关论文
共 47 条
[1]   SECONDARY STRUCTURE OF THE 5' NONTRANSLATED REGIONS OF HEPATITIS-C VIRUS AND PESTIVIRUS GENOMIC RNAS [J].
BROWN, EA ;
ZHANG, HC ;
PING, LH ;
LEMON, SM .
NUCLEIC ACIDS RESEARCH, 1992, 20 (19) :5041-5045
[2]   THE TAIWANESE HEPATITIS-C VIRUS GENOME - SEQUENCE DETERMINATION AND MAPPING THE 5' TERMINI OF VIRAL GENOMIC AND ANTIGENOMIC RNA [J].
CHEN, PJ ;
LIN, MH ;
TAI, KF ;
LIU, PC ;
LIN, CJ ;
CHEN, DS .
VIROLOGY, 1992, 188 (01) :102-113
[3]   ISOLATION OF A CDNA CLONE DERIVED FROM A BLOOD-BORNE NON-A, NON-B VIRAL-HEPATITIS GENOME [J].
CHOO, QL ;
KUO, G ;
WEINER, AJ ;
OVERBY, LR ;
BRADLEY, DW ;
HOUGHTON, M .
SCIENCE, 1989, 244 (4902) :359-362
[4]   COMPLETE 5' NONCODING REGION IS NECESSARY FOR THE EFFICIENT INTERNAL INITIATION OF HEPATITIS-C VIRUS-RNA [J].
FUKUSHI, S ;
KATAYAMA, K ;
KURIHARA, C ;
ISHIYAMA, N ;
HOSHINO, FB ;
ANDO, T ;
OYA, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 199 (02) :425-432
[5]   CHARACTERIZATION OF THE HEPATITIS-C VIRUS-ENCODED SERINE PROTEINASE - DETERMINATION OF PROTEINASE-DEPENDENT POLYPROTEIN CLEAVAGE SITES [J].
GRAKOUI, A ;
MCCOURT, DW ;
WYCHOWSKI, C ;
FEINSTONE, SM ;
RICE, CM .
JOURNAL OF VIROLOGY, 1993, 67 (05) :2832-2843
[6]   Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes [J].
Hanecak, R ;
BrownDriver, V ;
Fox, MC ;
Azad, RF ;
Furusako, S ;
Nozaki, C ;
Ford, C ;
Sasmor, H ;
Anderson, KP .
JOURNAL OF VIROLOGY, 1996, 70 (08) :5203-5212
[7]   PROTEOLYTIC PROCESSING AND MEMBRANE ASSOCIATION OF PUTATIVE NONSTRUCTURAL PROTEINS OF HEPATITIS-C VIRUS [J].
HIJIKATA, M ;
MIZUSHIMA, H ;
TANJI, Y ;
KOMODA, Y ;
HIROWATARI, Y ;
AKAGI, T ;
KATO, N ;
KIMURA, K ;
SHIMOTOHNO, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (22) :10773-10777
[8]  
Honda M, 1996, RNA, V2, P955
[9]   Structural requirements for initiation of translation by internal ribosome entry within genome-length hepatitis C virus RNA [J].
Honda, M ;
Ping, LH ;
Rijnbrand, RCA ;
Amphlett, E ;
Clarke, B ;
Rowlands, D ;
Lemon, SM .
VIROLOGY, 1996, 222 (01) :31-42
[10]   TRANSGENIC MICE CARRYING THE HUMAN POLIOVIRUS RECEPTOR - NEW ANIMAL-MODEL FOR STUDY OF POLIOVIRUS NEUROVIRULENCE [J].
HORIE, H ;
KOIKE, S ;
KURATA, T ;
SATOYOSHIDA, Y ;
ISE, I ;
OTA, Y ;
ABE, S ;
HIOKI, K ;
KATO, H ;
TAYA, C ;
NOMURA, T ;
HASHIZUME, S ;
YONEKAWA, H ;
NOMOTO, A .
JOURNAL OF VIROLOGY, 1994, 68 (02) :681-688