Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/37011
Title: Targeting Cell Division Cycle 25 Homolog B To Regulate Influenza Virus Replication
Authors: Perwitasari, Olivia
Torrecilhas, Ana Claudia [UNIFESP]
Yan, Xiuzhen
Johnson, Scott
White, Caleb
Tompkins, S. Mark
Tripp, Ralph A.
Univ Georgia
Universidade Federal de São Paulo (UNIFESP)
Issue Date: 1-Dec-2013
Publisher: Amer Soc Microbiology
Citation: Journal of Virology. Washington: Amer Soc Microbiology, v. 87, n. 24, p. 13775-13784, 2013.
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.
URI: http://repositorio.unifesp.br/handle/11600/37011
ISSN: 0022-538X
Other Identifiers: http://dx.doi.org/10.1128/JVI.01509-13
Appears in Collections:Artigo

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