@article{7e59359821f9471b8d64d38fbfffdbcb,
title = "Protein Phosphatase-1 regulates Rift Valley fever virus replication",
abstract = "Rift Valley fever virus (RVFV), genus Phlebovirus family Bunyaviridae, is an arthropod-borne virus endemic throughout sub-Saharan Africa. Recent outbreaks have resulted in cyclic epidemics with an increasing geographic footprint, devastating both livestock and human populations. Despite being recognized as an emerging threat, relatively little is known about the virulence mechanisms and host interactions of RVFV. To date there are no FDA approved therapeutics or vaccines for RVF and there is an urgent need for their development. The Ser/Thr protein phosphatase 1 (PP1) has previously been shown to play a significant role in the replication of several viruses. Here we demonstrate for the first time that PP1 plays a prominent role in RVFV replication early on during the viral life cycle. Both siRNA knockdown of PP1α and a novel PP1-targeting small molecule compound 1E7-03, resulted in decreased viral titers across several cell lines. Deregulation of PP1 was found to inhibit viral RNA production, potentially through the disruption of viral RNA transcript/protein interactions, and indicates a potential link between PP1α and the viral L polymerase and nucleoprotein. These results indicate that PP1 activity is important for RVFV replication early on during the viral life cycle and may prove an attractive therapeutic target.",
keywords = "Antiviral agent, Bunyaviridae, L polymerase, Phosphorylation, Protein phosphatase 1, Rift valley fever virus",
author = "Alan Baer and Nazly Shafagati and Ashwini Benedict and Tatiana Ammosova and Andrey Ivanov and Hakami, {Ramin M.} and Kaori Terasaki and Shinji Makino and Sergei Nekhai and Kylene Kehn-Hall",
note = "Funding Information: This project was supported by NIH Research Grants 1R15AI100001-01A1 (to KK), AI101772 (to SM), AI117445 (to SM), P50HL118006 (to SN), 5G12MD007597 (to SN), U19 AI109664-01 (to SN) and District of Columbia Center for AIDS Research grant ( 1P30AI117970 ) (to SN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: The authors thank Dr. Sina Bavari (USAMRIID) for providing RVFV MP-12 strain, Dr. Connie Schmaljohn (USAMRIID) for the RVFV N protein antibody, and Dr. Alejandro Brun for the pCMV-N plasmid construct. Influenza (A/2009H1N1) was obtained through BEI Resources, NIAID, NIH: Influenza A Virus, A/California/04/2009 (H1N1)pdm09, Cell Isolate (Produced in Cells), NR-13658. This project was supported by NIH Research Grants 1R15AI100001-01A1 (to KK), AI101772 (to SM), AI117445 (to SM), P50HL118006 (to SN), 5G12MD007597 (to SN), U19 AI109664-01 (to SN) and District of Columbia Center for AIDS Research grant (1P30AI117970) (to SN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2016 Elsevier B.V.",
year = "2016",
month = mar,
day = "1",
doi = "10.1016/j.antiviral.2016.01.007",
language = "English (US)",
volume = "127",
pages = "79--89",
journal = "Antiviral research",
issn = "0166-3542",
publisher = "Elsevier",
}