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

J. Biol. Chem., Vol. 276, Issue 26, 24301-24308, June 29, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/26/24301    most recent M010806200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Romeo, A. M. Articles by Kosman, D. J. Search for Related Content PubMed PubMed Citation Articles by Romeo, A. M. Articles by Kosman, D. J. Social Bookmarking                      What's this?

Intracellular Chelation of Iron by Bipyridyl Inhibits DNA Virus Replication
RIBONUCLEOTIDE REDUCTASE MATURATION AS A PROBE OF INTRACELLULAR IRON POOLS^*

Annette M. Romeo, Linda Christen, Edward G. Niles, and Daniel J. Kosman

From the Departments of Biochemistry and Microbiology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York 14214

The efficient replication of large DNA viruses requires dNTPs supplied by a viral ribonucleotide reductase. Viral ribonucleotide reductase is an early gene product of both vaccinia and herpes simplex virus. For productive infection, the apoprotein must scavenge iron from the endogenous, labile iron pool(s). The membrane-permeant, intracellular Fe²⁺ chelator, 2,2'-bipyridine (bipyridyl, BIP), is known to sequester iron from this pool. We show here that BIP strongly inhibits the replication of both vaccinia and herpes simplex virus, type 1. In a standard plaque assay, 50 µM BIP caused a 50% reduction in plaque-forming units with either virus. Strong inhibition was observed only when BIP was added within 3 h post-infection. This time dependence was observed also in regards to inhibition of viral late protein and DNA synthesis by BIP. BIP did not inhibit the activity of vaccinia ribonucleotide reductase (RR), its synthesis, nor its stability indicating that BIP blocked the activation of the apoprotein. In parallel with its inhibition of vaccinia RR activation, BIP treatment increased the RNA binding activity of the endogenous iron-response protein, IRP1, by 1.9-fold. The data indicate that the diiron prosthetic group in vaccinia RR is assembled from iron taken from the BIP-accessible, labile iron pool that is sampled also by ferritin and the iron-regulated protein found in the cytosol of mammalian cells.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				W. E. Crowe, L. M. Maglova, P. Ponka, and J. M. Russell Human cytomegalovirus-induced host cell enlargement is iron dependent Am J Physiol Cell Physiol, October 1, 2004; 287(4): C1023 - C1030. [Abstract] [Full Text] [PDF]

				N. Surguladze, K. M. Thompson, J. L. Beard, J. R. Connor, and M. G. Fried Interactions and Reactions of Ferritin with DNA J. Biol. Chem., April 9, 2004; 279(15): 14694 - 14702. [Abstract] [Full Text] [PDF]