Herpes simplex virus virion host shutoff protein is stimulated by translation initiation factors eIF4B and eIF4H

被引:57
作者
Doepker, RC [1 ]
Hsu, WL [1 ]
Saffran, HA [1 ]
Smiley, JR [1 ]
机构
[1] Univ Alberta, Heritage Med Res Ctr 632, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2S2, Canada
关键词
D O I
10.1128/JVI.78.9.4684-4699.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The virion host shutoff protein (vhs) of herpes simplex virus triggers accelerated degradation of cellular and viral mRNAs while sparing other cytoplasmic RNA species. Previous work has shown that vhs forms a complex with translation initiation factor eIF4H, which displays detectable RNase activity in the absence of other viral or host proteins. However, the contributions of eIF4H and other host factors to the activity and mRNA targeting properties of vhs have not yet been directly examined. An earlier report from our laboratory demonstrated that rabbit reticulocyte lysate (RRL) contains one or more factors that strongly stimulate the RNase activity of vhs produced in Saccharomyces cerevisiae. We report here that such yeast extracts display significant vhs-dependent RNase activity in the absence of mammalian factors. This activity differs from that displayed by vhs generated in RRL in that it is not targeted to the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES). Activity was strongly enhanced by the addition of RRL, eIF4H, or the related translation factor eIF4B. RRL also reconstituted strong targeting to the EMCV IRES, resulting in a major change in the RNA cleavage pattern. In contrast, eIF4H and eIF4B did not reconstitute IRES-directed targeting. These data indicate that eIF4B and 4H stimulate the nuclease activity of vhs, and they provide evidence that additional mammalian factors are required for targeting to the EMCV IRES.
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页码:4684 / 4699
页数:16
相关论文
共 68 条
[1]   A SACCHAROMYCES-CEREVISIAE HOMOLOG OF MAMMALIAN TRANSLATION INITIATION FACTOR-4B CONTRIBUTES TO RNA HELICASE ACTIVITY [J].
ALTMANN, M ;
MULLER, PP ;
WITTMER, B ;
RUCHTI, F ;
LANKER, S ;
TRACHSEL, H .
EMBO JOURNAL, 1993, 12 (10) :3997-4003
[2]   A NEW YEAST TRANSLATION INITIATION-FACTOR SUPPRESSES A MUTATION IN THE ELF-4A RNA HELICASE [J].
COPPOLECCHIA, R ;
BUSER, P ;
STOTZ, A ;
LINDER, P .
EMBO JOURNAL, 1993, 12 (10) :4005-4011
[3]   The helix-hairpin-helix DNA-binding motif: A structural basis for non-sequence-specific recognition of DNA [J].
Doherty, AJ ;
Serpell, LC ;
Ponting, CP .
NUCLEIC ACIDS RESEARCH, 1996, 24 (13) :2488-2497
[4]   The herpes simplex virus vhs protein induces endoribonucleolytic cleavage of target RNAs in cell extracts [J].
Elgadi, MM ;
Hayes, CE ;
Smiley, JR .
JOURNAL OF VIROLOGY, 1999, 73 (09) :7153-7164
[5]   Picornavirus internal ribosome entry site elements target RNA cleavage events induced by the herpes simplex virus virion host shutoff protein [J].
Elgadi, MM ;
Smiley, JR .
JOURNAL OF VIROLOGY, 1999, 73 (11) :9222-9231
[6]   Mutational analysis of the virion host shutoff gene (UL41) of herpes simplex virus (HSV): Characterization of HSV type 1 (HSV-1)/HSV-2 chimeras [J].
Everly, DN ;
Read, GS .
JOURNAL OF VIROLOGY, 1997, 71 (10) :7157-7166
[7]   mRNA degradation by the virion host shutoff (Vhs) protein of herpes simplex virus: Genetic and biochemical evidence that Vhs is a nuclease [J].
Everly, DN ;
Feng, PH ;
Mian, IS ;
Read, GS .
JOURNAL OF VIROLOGY, 2002, 76 (17) :8560-8571
[8]   INTERNAL RIBOSOME ENTRY SITE OF ENCEPHALOMYOCARDITIS VIRUS-RNA IS UNABLE TO DIRECT TRANSLATION IN SACCHAROMYCES-CEREVISIAE [J].
EVSTAFIEVA, AG ;
BELETSKY, AV ;
BOROVJAGIN, AV ;
BOGDANOV, AA .
FEBS LETTERS, 1993, 335 (02) :273-276
[9]   MRNA decay during herpesvirus infections: Interaction between a putative viral nuclease and a cellular translation factor [J].
Feng, PH ;
Everly, DN ;
Read, GS .
JOURNAL OF VIROLOGY, 2001, 75 (21) :10272-10280
[10]  
FENG WC, 1994, J BIOL CHEM, V269, P1493