HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lanke, K. Articles by van Kuppeveld, F. J. M. Search for Related Content PubMed PubMed Citation Articles by Lanke, K. Articles by van Kuppeveld, F. J. M. Agricola Articles by Lanke, K. Articles by van Kuppeveld, F. J. M.

PDTC inhibits picornavirus polyprotein processing and RNA replication by transporting zinc ions into cells

¹ Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands
² Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Medical University of Vienna, Dr Bohr Gasse 9/3, A-1030 Vienna, Austria

Correspondence
F. J. M. van Kuppeveld
f.vankuppeveld{at}ncmls.ru.nl

Previously, it was shown that pyrrolidine dithiocarbamate (PDTC) inhibits proteolytic polyprotein processing and replication of human rhinovirus by transporting metal ions into cells. Here, it is shown that PDTC also inhibits replication of two other picornaviruses: coxsackievirus B3 (CVB3), a closely related virus that belongs to the genus Enterovirus, and mengovirus, an encephalomyocarditis virus strain that belongs to the genus Cardiovirus, and that this inhibition is due to the dithiocarbamate moiety of the compound. Making use of subgenomic replicons, evidence is provided that PDTC inhibits replication of these two viruses by disturbing viral RNA synthesis. Furthermore, it is shown that PDTC transports zinc ions into cells and that these zinc ions play an important role in the antiviral activity mediated by PDTC. Finally, it is shown that PDTC interferes with proteolytic processing of the polyproteins of both CVB3 and mengovirus, but that the underlying mechanism between these two viruses differs. In CVB3-infected cells, PDTC interferes strongly with the proteolytic activity of 3CD^pro, as shown by the impaired production of the mature capsid proteins as well as the autocleavage of 3CD^pro into 3C^pro and 3D^pol. In mengovirus-infected cells, however, PDTC had no effect on the proteolytic production of capsid proteins or the autocleavage of 3CD^pro. Instead, PDTC caused the accumulation of a high-molecular-mass precursor protein, due to an impairment in the primary ‘break’ that normally occurs at the 2A–2B junction. Thus, PDTC disturbs polyprotein processing and replication of two groups of picornaviruses, enteroviruses and cardioviruses, but the underlying mechanism is different.

This article has been cited by other articles:

				M. Arita, T. Wakita, and H. Shimizu Cellular kinase inhibitors that suppress enterovirus replication have a conserved target in viral protein 3A similar to that of enviroxime J. Gen. Virol., August 1, 2009; 90(8): 1869 - 1879. [Abstract] [Full Text] [PDF]

				B. M. Krenn, E. Gaudernak, B. Holzer, K. Lanke, F. J. M. Van Kuppeveld, and J. Seipelt Antiviral Activity of the Zinc Ionophores Pyrithione and Hinokitiol against Picornavirus Infections J. Virol., January 1, 2009; 83(1): 58 - 64. [Abstract] [Full Text] [PDF]