Targeting Cell Division Cycle 25 Homolog B To Regulate Influenza Virus Replication

Targeting Cell Division Cycle 25 Homolog B To Regulate Influenza Virus Replication

Author Perwitasari, Olivia Google Scholar
Torrecilhas, Ana Claudia Autor UNIFESP Google Scholar
Yan, Xiuzhen Google Scholar
Johnson, Scott Google Scholar
White, Caleb Google Scholar
Tompkins, S. Mark Google Scholar
Tripp, Ralph A. Google Scholar
Institution Univ Georgia
Universidade Federal de São Paulo (UNIFESP)
Abstract Influenza virus is a worldwide global health concern causing seasonal morbidity mortality and economic burden. Chemotherapeutics is available; however, rapid emergence of drug-resistant influenza virus strains has reduced its efficacy. Thus, there is a need to discover novel antiviral agents. in this study, RNA interference (RNAi) was used to screen host genes required for influenza virus replication. One pro-influenza virus host gene identified was dual-specificity phosphatase cell division cycle 25 B (CDC25B). RNAi screening of CDC25B resulted in reduced influenza A virus replication, and a CDC25B small-molecule inhibitor (NSC95397) inhibited influenza A virus replication in a dose-dependent fashion. Viral RNA synthesis was reduced by NSC95397 in favor of increased beta interferon (IFN-beta) expression, and NSC95397 was found to interfere with nuclear localization and chromatin association of NS1, an influenza virus protein. As NS1 has been shown to be chromatin associated and to suppress host transcription, it is likely that CDC25B supports NS1 nuclear function to hijack host transcription machinery in favor of viral RNA synthesis, a process that is blocked by NSC95397. Importantly, NSC95397 treatment protects mice against lethal influenza virus challenge. the findings establish CDC25B as a pro-influenza A virus host factor that may be targeted as a novel influenza A therapeutic strategy.
Language English
Sponsor National Institutes of Health, National Institute of Allergy and Infectious Diseases
Georgia Research Alliance
Grant number National Institutes of Health, National Institute of Allergy and Infectious Diseases: HHSN266200700006C
Date 2013-12-01
Published in Journal of Virology. Washington: Amer Soc Microbiology, v. 87, n. 24, p. 13775-13784, 2013.
ISSN 0022-538X (Sherpa/Romeo, impact factor)
Publisher Amer Soc Microbiology
Extent 13775-13784
Origin http://dx.doi.org/10.1128/JVI.01509-13
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000327443300063
URI http://repositorio.unifesp.br/handle/11600/37011

Show full item record




File

Name: WOS000327443300063.pdf
Size: 1.809Mb
Format: PDF
Description:
Open file

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account