This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fukui, Y.
Right arrow Articles by Inoue, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fukui, Y.
Right arrow Articles by Inoue, N.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 2008, p. 2420-2427, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.00134-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Establishment of a Cell-Based Assay for Screening of Compounds Inhibiting Very Early Events in the Cytomegalovirus Replication Cycle and Characterization of a Compound Identified Using the Assay{triangledown}

Yoshiko Fukui,1 Keiko Shindoh,1,2 Yumiko Yamamoto,1 Shin Koyano,3 Isao Kosugi,4 Toyofumi Yamaguchi,2 Ichiro Kurane,1 and Naoki Inoue1*

Department of Virology I, National Institute of Infectious Diseases, Tokyo,1 Department of Biosciences, Teikyo University of Science and Technology, Yamanashi,2 Department of Pediatrics, Asahikawa Medical College, Hokkaido,3 Department of Pathology II, Hamamatsu Medical University, Shizuoka, Japan4

Received 30 January 2008/ Returned for modification 2 April 2008/ Accepted 30 April 2008

To simplify the detection of infectious human cytomegalovirus (HCMV), we generated a cell line that produced luciferase in a dose-dependent manner upon HCMV infection. Using this cell line, we identified anti-HCMV compounds from a diverse library of 9,600 compounds. One of them, 1-(3,5-dichloro-4-pyridyl)piperidine-4-carboxamide (DPPC), was effective against HCMV (Towne strain) infection of human lung fibroblast cells at a 50% effective concentration of 2.5 µM. DPPC also inhibited the growth of clinical HCMV isolates and guinea pig and mouse cytomegaloviruses. Experiments using various time frames for treatment of the cells with DPPC demonstrated that DPPC was effective during the first 24 h after HCMV infection. DPPC treatment decreased not only viral DNA replication but also IE1 and IE2 expression at mRNA and protein levels in the HCMV-infected cells. However, DPPC did not inhibit the attachment of HCMV particles to the cell surface. DPPC is a unique compound that targets the very early phase of cytomegalovirus infection, probably by disrupting a pathway that is important after viral entry but before immediate-early gene expression.

* Corresponding author. Mailing address: Laboratory of Herpesviruses, Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: 81-3-5285-1111, ext. 2528. Fax: 81-3-5285-1180. E-mail: ninoue{at}nih.go.jp

{triangledown} Published ahead of print on 5 May 2008.

Antimicrobial Agents and Chemotherapy, July 2008, p. 2420-2427, Vol. 52, No. 7
0066-4804/08/$08.00+0     doi:10.1128/AAC.00134-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»