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Journal of Virology, November 2004, p. 12075-12081, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.12075-12081.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Differential Effects on the Hepatitis C Virus (HCV) Internal Ribosome Entry Site by Vitamin B12 and the HCV Core Protein

Dongsheng Li,1,2 William B. Lott,3 John Martyn,1 Gholamreza Haqshenas,1 and Eric J. Gowans1*

Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria,1 School of Molecular & Microbial Sciences, University of Queensland, St. Lucia, Queensland, Australia,2 Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, New Mexico3

Received 4 January 2004/ Accepted 18 June 2004

To investigate the role of the hepatitis C virus internal ribosome entry site (HCV IRES) domain IV in translation initiation and regulation, two chimeric IRES elements were constructed to contain the reciprocal domain IV in the otherwise HCV and classical swine fever virus IRES elements. This permitted an examination of the role of domain IV in the control of HCV translation. A specific inhibitor of the HCV IRES, vitamin B12, was shown to inhibit translation directed by all IRES elements which contained domain IV from the HCV and the GB virus B IRES elements, whereas the HCV core protein could only suppress translation from the wild-type HCV IRES. Thus, the mechanisms of translation inhibition by vitamin B12 and the core protein differ, and they target different regions of the IRES.

* Corresponding author. Mailing address: Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne, VIC 3001, Australia. Phone: 61 03 9282 2204. Fax: 61 03 9282 2100. E-mail: gowans{at}burnet.edu.au.

Journal of Virology, November 2004, p. 12075-12081, Vol. 78, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.21.12075-12081.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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