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Journal of Virology, May 2004, p. 4487-4497, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4487-4497.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Functional and Structural Similarities between the Internal Ribosome Entry Sites of Hepatitis C Virus and Porcine Teschovirus, a Picornavirus

Andrey V. Pisarev,1 Louisa S. Chard,2 Yoshihiro Kaku,3 Helen L. Johns,2 Ivan N. Shatsky,1 and Graham J. Belsham2*

Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899, Russia,1 BBSRC Institute for Animal Health, Pirbright, Woking, Surrey GU24 ONF, United Kingdom,2 Department of Exotic Diseases, National Institute of Animal Health, 6-20-1 Josuihoncho, Kodaira, Tokyo 187-0022, Japan3

Received 17 September 2003/ Accepted 8 January 2004

Initiation of protein synthesis on picornavirus RNA requires an internal ribosome entry site (IRES). Typically, picornavirus IRES elements contain about 450 nucleotides (nt) and use most of the cellular translation initiation factors. However, it is now shown that just 280 nt of the porcine teschovirus type 1 Talfan (PTV-1) 5' untranslated region direct the efficient internal initiation of translation in vitro and within cells. In toeprinting assays, assembly of 48S preinitiation complexes from purified components on the PTV-1 IRES was achieved with just 40S ribosomal subunits plus eIF2 and Met-tRNAiMet. Indeed, a binary complex between 40S subunits and the PTV-1 IRES is formed. Thus, the PTV-1 IRES has properties that are entirely different from other picornavirus IRES elements but highly reminiscent of the hepatitis C virus (HCV) IRES. Comparison between the PTV-1 IRES and HCV IRES elements revealed islands of high sequence identity that occur in regions critical for the interactions of the HCV IRES with the 40S ribosomal subunit and eIF3. Thus, there is significant functional and structural similarity between the IRES elements from the picornavirus PTV-1 and HCV, a flavivirus.

* Corresponding author. Mailing address: BBSRC Institute for Animal Health, Pirbright Lab, Ash Rd., Pirbright, Woking GU24 ONF, United Kingdom. Phone: 44(0)1483-232441. Fax: 44(0)1483-232448. E-mail: graham.belsham{at}bbsrc.ac.uk.

Journal of Virology, May 2004, p. 4487-4497, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4487-4497.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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