Journal article
Curcumin Inhibits Rift Valley Fever Virus Replication in Human Cells
The Journal of biological chemistry, v 287(40), pp 33198-33214
28 Sep 2012
PMID: 22847000
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Rift Valley fever virus (RVFV) is an arbovirus that is classified as a select agent, an emerging infectious virus, and an agricultural pathogen. Understanding RVFV-host interactions is imperative to the design of novel therapeutics. Here, we report that an infection by the MP-12 strain of RVFV induces phosphorylation of the p65 component of the NF kappa B cascade. We demonstrate that phosphorylation of p65 (serine 536) involves phosphorylation of I kappa B alpha and occurs through the classical NF kappa B cascade. A unique, low molecular weight complex of the IKK-beta subunit can be observed in MP-12-infected cells, which we have labeled IKK-beta 2. The IKK-beta 2 complex retains kinase activity and phosphorylates an I kappa B alpha substrate. Inhibition of the IKK complex using inhibitors impairs viral replication, thus alluding to the requirement of an active IKK complex to the viral life cycle. Curcumin strongly down-regulates levels of extracellular infectious virus. Our data demonstrated that curcumin binds to and inhibits kinase activity of the IKK-beta 2 complex in infected cells. Curcumin partially exerts its inhibitory influence on RVFV replication by interfering with IKK-beta 2-mediated phosphorylation of the viral protein NSs and by altering the cell cycle of treated cells. Curcumin also demonstrated efficacy against ZH501, the fully virulent version of RVFV. Curcumin treatment down-regulated viral replication in the liver of infected animals. Our data point to the possibility that RVFV infection may result in the generation of novel versions of host components (such as IKK-beta 2) that, by virtue of altered protein interaction and function, qualify as unique therapeutic targets.
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Details
- Title
- Curcumin Inhibits Rift Valley Fever Virus Replication in Human Cells
- Creators
- Aarthi Narayanan - George Mason UniversityKylene Kehn-Hall - George Mason UniversitySvetlana Senina - George Mason UniversityLindsay Lundberg - George Mason UniversityRachel Van Duyne - George Mason UniversityIrene Guendel - George Mason UniversityRavi Das - George Mason UniversityAlan Baer - George Mason UniversityLaura Bethel - University of PittsburghMichael Turell - United States Army Medical Research Institute of Infectious DiseasesAmy Lynn Hartman - University of PittsburghBhaskar Das - Albert Einstein College of MedicineCharles Bailey - George Mason UniversityFatah Kashanchi - George Mason University
- Publication Details
- The Journal of biological chemistry, v 287(40), pp 33198-33214
- Publisher
- Elsevier
- Number of pages
- 17
- Grant note
- DE-FC52-04NA25455 / United States Department of Energy; United States Department of Energy (DOE)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000309602100011
- Scopus ID
- 2-s2.0-84866954267
- Other Identifier
- 991021902519204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology